Background/aims: The importance of dietary fish oil is a well-known concept in the treatment of inflammatory bowel disease, but there are few reports indicating the effect of fish oil enema in the treatment of this disease. The aim of this study was to investigate the protective role of fish oil in acetic acid and ethanol induced colonic injury. Methods: Sixty male Wistar rats were equally divided into six groups. Following rectal administration of 1 ml of placebo (group 1), fish oil (group 2) and corn oil (group 3), 4% acetic acid was given via the same route to these groups. The former procedure was repeated in groups 4, 5 and 6 (placebo, fish oil and corn oil respectively), followed by rectal administration of 0.25 ml of 30% ethanol. The level of leukotriene B4, histopathologic scores and myeloperoxidase activity were then determined in the colonic mucosa. Results: Levels of leukotriene B4 and myeloperoxidase activity were significantly reduced by fish oil enema in both the acetic acid and ethanol groups. However, they were not found to be significantly reduced in the placebo and corn oil groups. Conclusions: It is concluded that fish oil enema has a protective role in acetic acid induced and ethanol induced colonic injury in rats.