It has been demonstrated that nonsteroidal anti-inflammatory drug (NSAID)’s releasing prostaglandin inhibition, created some degree of suppression in the carcinogenesis of the colon. Many recent studies have been directed to underline the mechanism of the preventive effect of NSAID’s and especially aspirin in colonic carcinogenesis. The most frequent subject among these studies is the mutagenic effect of arachidonic acid metabolites. Malondialdehyde (MDA) is the product of arachidonic acid metabolism whose mutagenic effect has been shown, and MDA production can be prevented by cyclooxygenase inhibition. We performed an experimental study to demonstrate the effect of aspirin on the tissue MDA in colonic carcinogenesis. The study is built into four groups, consisting of ten rats each. Group 1: Control group; serum physiologic group, equal volumes to azoxymethane (AOM) is given two weeks subcutaneously, once every week. Group 2: AOM group; 15 mg/kg/week AOM is given subcutaneously for two weeks. Group 3: AOM + 1.4 mg/kg/day aspirin group; following the last dose of AOM, 1.4 mg/kg/day aspirin added to daily fluid doses. Group 4: AOM +5 mg/kg/day Aspirin group; following the last dose of AOM 5 mg/kg/day aspirin is added to the daily fluid doses. Fifty-two weeks after the last AOM dose laparotomy was performed on all the rats. The number, location, and dimension of all two moral masses in all groups were examined. Tumor volumes were calculated. The histopathologic examinations were done and both of the tumor and normal mucosa MDA measures were studied. According to the results, mucosa MDA measures were significantly higher in the other groups than group 1 (p<0.05). On the other hand, there was a significant difference between groups 2-4 (p=0.03) whether there wasn’t a significant difference between groups 2 and 3. When tumor MDA measures have been studied, there wasn’t a difference between 2 and 3, but the measures which have been established for group 4 were lower than either in group 2 or group 3 (p=0.02, p=0.001). Tumor volumes in group 2 were significantly higher than both of group 3 and group 4 (p=0.0009, p=0.0012). These results demonstrate that NSAIDs and aspirin have prevention effects on colonic carcinogenesis. However, there is no agreement about how the drugs affect the carcinogenesis. In this study, decreasing mutagenic activity which is linked to MDA, is one of the mechanisms that has been proved. Furthermore, it has been showed that this effect happens at anti analgesic doses