This blinded study describes the effect of ibuprofen (IBU) on experimental pressure ulcers (PU) induced in the fuzzy rat model. Ibuprofen's fibrinolytic activity has been found effective in preserving dermal vasculature in rats following burn injury. Experimental pressure ulcers were generated on the hips of fuzzy rats with the aid of computer control, using five daily, 6-hour pressure sessions. In the first study, 17 rats received intraperitoneal (I.P.) injection of IBU or saline control after each pressure session. In the second study, 44 rats received IBU or control, before, during, and after application of pressure by I.P. or intramuscular (I.M.) injections. Quantitation of histology is based on five prominent lesions, including: ulceration, infarction, panniculus carnosus necrosis, fat atrophy, and deep muscle necrosis. The following hypothesis was tested: Reperfusion injury and vascular occlusion in pressure ulcers may be similar to that which occurs in burns and, therefore, is responsive to IBU intervention. The results indicate that IBU does not have significant effects on the development of pressure ulcers. The mechanisms of IBU action in other organ and tissue systems are discussed in relation to the effect of IBU on the pressure ulcer model.