In 1878 the State College of Kentucky was separated from the Agricultural and Mechanical College. James Patterson became the first president of the State College, which subsequently became the University of Kentucky. In 1890, Joseph William Pryor was hired as the chair of the department of anatomy and physiology. Pryor was trained as an MD and he had a significant interest in the preparation of undergraduates for medical school. He instituted a pre-medical curriculum and began to teach pre-medical courses long before the Flexner Report of 1910 altered medical education throughout the country. 

Pryor retired in 1931 although he continued to publish until he was 90! He was succeeded as chairman by Richard S. Allen. During the Great Depression, there was little funding and almost no research thus the department languished. In the late 40s James Archdeacon and Louis L. Boyarsky were hired to promote research. 

During the 1950s there was an active move to create a medical school in Lexington to serve the eastern part of the state. The development of this school was championed by the governor of Kentucky, Albert B. Chandler. The A.B. Chandler Medical School was authorized by the board of trustees in 1956 and William Willard was hired as vice-president for the Medical Center. As a result of this reorganization, Loren D. Carlson was hired to chair the newly created department of physiology and biophysics. R.S. Allen, Archdeacon and Boyarsky were absorbed into the new department. Dr. Carlson hired a number of new scientists in the early 1960s including Joseph Engelberg (cell biology and biophysics; 1961-1994), David Merigian (neurophysiology; 1960-1961), Dennis Galvin (1960-1962), Judith Pratt (1960-1981), Fred Zechman (respiration; 1961-1965), James Zolman (physiological physiology; 1964-2001), and Ernest McCutcheon (cardiovascular; 1966-1974).

The rapid growth in faculty was supported by both local and national sources. With these resources, the department developed a strong doctoral program with an emphasis on individualized instruction. Advanced courses in systems physiology, quantitative analysis and biophysics were developed around the unifying conceptual thread of physiological systems control. When Carlson left in 1966 to become the chief of basic sciences at Davis, California, Dr. Boyarsky served as the acting chair for two years. In 1968, Fred Zechman was appointed chair and the department experienced considerable growth, growing from 9 faculty to 17. The new hires included: Donald Frazier (neurophysiology of respiration; 1969-2001), Bertram Peretz (neurophysiology; 1969-2001), Daniel Richardson (circulation; 1970-2004), Barbara Birge (undergraduate teaching; 1971-2002), David Lally (respiration; 1973-78), Cobern Ott (renal;1975-2005), David Randall (cardiovascular; 1975-2018), Lu-Yuan Lee (respiration; 1978-present), and Sandra Legan (endocrinology; 1978-2018). This period was marked by increased collaboration with both clinical and basic science departments, program project grants, and increased national funding. 

In 1980, Dr. Zechman resigned his position as chair to become the associate dean for research and graduate studies. He was succeeded by Dr. Donald Frazier who was the second doctoral student graduated from this department (under the mentorship of Lou Boyarsky). Under Frazier, the department continued to experience significant growth through the addition of faculty in research and regular title lines, as well as collaborative efforts with the Tobacco and Healthy Research Institute and joint appointees. Most of the faculty increased the strength and profile of the department as a nationally recognized leader in cardiovascular and respiratory-related areas. Faculty joining the department included: Brian Jackson (renal; 1981- present), Dexter Speck (control of respiration; 1984-2022), John Diana (cardiovascular; 1985-1990), Cheryl Heesch (cardiovascular; 1985-1990, Rob Revelette (respiration; 1986-1990), Thomas Dowell (cardiovascular; 1989-1995), Thomas Getchell (sensory; 1989-2013), Ronald Fiscus (circulation; 1990-1994), and Doug McMahon (neurophysiology; 1990-2002).

Dr. Frazier resigned as chair in 1992 and Dr. Wekstein was appointed as acting chair while a national search was conducted with the intention of strengthening the department in the area of molecular physiology. Phyllis Wise was selected as chair and she served from 1993-2001. Under her direction the department continued to grow and several additional regular faculty lines were created. The recruitment of research faculty and collaborative arrangements with centers such as Aging and Spinal Cord further expanded the faculty ranks. With a growing strength in molecular physiology and a decrease in the area of biophysics, the name was changed to simply the department of physiology. New faculty included: Jeff Falcone (circulation; 1993-1995), Ok-Kyong Park-Sarge (reproductive endocrinology; 1994-present), Tim McClintock (olfaction; 1994-present), Steve Estus (neurophysiology; 1994-present), Jon Satin (channels; 1994-present), Fadi Xu (respiration; 1995-2002), Eric Smart (caveoli; 1996-2003), Marianna Karakasian (sphingolipids, 1998-present), Malathi Srivatsan (neurophysiology; 1998-2003), George Smith (spinal cord regeneration; 1999-2009), Lei Li (1999-2003), Ming Gong (circulation; 1999-present), Scott Diamond (endocrinology; 2000-2010), and Rodney Guttman (neurophysiology; 2001-2010).

With the resignation of Dr. Wise, Dr. Jackson was appointed as acting chair and Alexander Rabchevsky (spinal cord regeneration, 2002-present), Kathy Saatman (neuronal cytoskeleton, 2002-present) and Melinda Wilson (endocrinology, 2001–present) were hired. With the addition of Michael Reid as departmental chair in 2003, several faculty were added in the area of muscle physiology. Karyn Esser (2004-2015), Ken Campbell (2004-2022), and Francisco Andrade (2004-present) joined the department in 2004 establishing a strong muscle physiology group.   A large number of faculty from other areas were also added.  These faculty include Gregory Frolekov (inner ear mechanosensitivity, 2005-present), Brian Delisle (cardiovascular, 2007-present), Bret Smith (epilepsy, 2007-2018 [to become chair of department of neuroscience]), Bradley Taylor (chronic pain, 2007-2018), Joe Abisambra (Alzheimer’s and aging, 2013-2018), and Moriel Vandsburger (cardiovascular imaging, 2013-2016).

In 2013, Dr. Reid left the department for a dean’s position at the University of Florida.  After his departure, Dr. Andrade filled in as interim chair until Dr. Alan Daugherty was appointed chair in 2015. Since Dr. Daugherty's appointment, the department added both junior and senior faculty alike to its ranks. From 2016-2020, the department would welcome 9 new faculty: Lance Johnson (ApoE, brain metabolism and cognition, 2016-present), Chris Waters (lung injury, 2017-present), Xiang-an Li (HDL metabolism,2017-present), Erhard Bieberich (sphingolipid ceramide, 2017-present), Alejandra Catalina Vélez-Ortega (inner ear, 2018-present), Ryan Temel (2018-present), Venkateswaran Subramanian (aortic vascular disease and obesity, 2018-2022), Scott Gordon (metabolism and atherosclerotic cardiovascular disease, 2018-present), Hong Lu (Renin angiotensin system related mechanisms of atherosclerosis, 2019-present), Thad Wilson (skin and temperature regulation, 2020-present), and Gregory Graf (lipoprotein metabolism 2022-present).  More recently, the department has added several junior faculty including Shannon Macauley (brain metabolism and cognition, 2023 - present), Brad Hubbard (pathobiology of traumatic brain injury, 2023 - present), Samir Patel (mitochondria focused neurotherapeutics for spinal cord injury, 2023 - present), Yuan Wen (muscle biology, 2023 - present) and Cheavar Blair (mechanical function of cardiomyocytes, 2023 - present)

As of January 2024, the department has 50 affiliated faculty:  36 primary and 14 secondary faculty. Combined their experience covers a wide gamut of subjects and expertise.

In addition to outstanding contributions in research, the department has an exceptional reputation of training graduate students for the biomedical sciences workforce. From 2017-2022, the department maintained a graduate student population of 22.5 students at the start of each academic year and graduated around 5 before the end of the academic year. The average time to PhD being 4.8 years. The majority of the trainee population is mostly comprised of individuals that matriculated through the Integrated Biomedical Sciences program (IBS), however also included are those enrolled in the MD/PhD Program, as well as direct admissions. 

Currently, the department also has a large presence on multiple education fronts. Physiology faculty are heavily involved in undergraduate, graduate, and professional level courses, including course directing several MD courses. With this extraordinary level of effort, physiology faculty have participated in the education of an estimated 2,000+ students each academic year.