Purpose: In this experimental study, the role of allopurinol - xanthine oxidase inhibitor - and superoxide dismutase (SOD) - free radical scavenger - in the prevention of indomethacin-induced acute mucosal lesions were investigated. Methods: Thirty rats from both sexes weighing 90-130 gr. were used. Six of them were used to investigate the effect of 48 hours fasting on ulcer occurrence. In the control group (n = 8), subcutaneous indomethacin was administered to form acute mucosal lesion. Other two groups, each consisting of eight rats, were given SOD and allopurinol, respectively. Results: In the indomethacin group, the ulcer score was found to be 22.4 ± 2.8 mm., while it was 13.5 ± 2.5 mm. and 7.6 ± 3.0 mm. in the allopurinol and SOD group respectively. Compared with the control group, allopurinol and SOD groups were found to be statistically significant in reducing ulcer formation. Moreover, SOD was also found to be more effective than allopurinol in preventing ulcer formation. Conclusion: According to these results, it can be assumed that the free oxygen radicals (FOR) generated through the lipooxygenase and xanthine oxidase pathways have an important role in the pathogenesis of indomethacin-induced ulcer besides the other humoral mediators.