There is a growing body of evidence that implicates oxygen free radicals in a wide variety of inflammatory conditions in various body systems including the gastrointestinal tract. The purpose of this study was to ascertain whether or not oxy-radicals play a role in carrageenan-mediated intestinal injury. Allopurinol, superoxide dismutase-polyethylene glycol, and dimethyl sulfoxide, respectively, were administered to the carrageenan rat model for 30 to 32 days. Collectively, all three drugs attenuated the carrageenan-mediated injury as shown by four indices of intestinal damage: ulceration (p = 0.0007); abnormal villous pattern (p = 0.0002); degree of inflammation (p = 0.0001); and extent of inflammation (p = 0.0025). Dimethyl sulfoxide appeared to be the least efficacious of the three drugs. The results suggest that oxygen free radicals play a role in carrageenan-mediated intestinal injury, and that one of the sources of these oxy-radicals may be the intestinal macrophage.