Biol. Pharm. Bull. 28(8) 1321—1341 (2005)

“The most important undertaking in science is the establishment of experimental methods”—Ivan P. Pavlov (1849— 1936). Pavlov’s statement is readily applicable to ulcer research, i.e., establishing an experimental ulcer model that resembles human ulcers is of utmost importance. Nonetheless, although easily stated, developing an experimental method can prove difficult, especially when such a method lies beyond the frontiers of contemporary science. This review article describes the process underlying establishment of one such experimental method, namely how a chronic ulcer model, currently called the “acetic acid ulcer” model, was established in laboratory animals. Since its development in 1969, the acetic acid ulcer model has become well established in the scientific community. The number of published studies in which acetic acid ulcer models have been utilized numbers approximately 30—45 per year over the past decade. The reasons underlying the model’s frequent use as the chronic ulcer model of choice appear to be as follows. 1) The ulcer induction procedure is quite simple, readily resulting in ulcers of consistent size and severity at an incidence of 100%. 2) The ulcer models highly resemble human ulcers in terms of both pathological features and healing mechanisms. Indeed, spontaneous relapse of healed ulcers is frequently observed, just as in peptic ulcer patients. 3) The ulcers respond well to various anti-ulcer drugs, such as acid pump inhibitors, sucralfate, and several growth factors. Moreover, both steroidal and non-steroidal anti-inflammatory drugs negatively impact healing of the experimental ulcers. The ulcer models are now used as the standard model for screening compounds as potential anti-ulcer drugs. The below summarizes the history of the development, as well as the utility of acetic acid ulcer models. In addition, state of the art research concerning the mechanisms underlying the healing of acetic acid ulcers is overviewed.