Resveratrol is a natural polyphenol present in the Japanese knotweed. It exhibits variety of chemopreventive and anti-proliferative effects against the different cancer cell lines. During skin carcinogenesis, the radical scavenging activity gets altered which are important to prevent the deleterious effect of free radicals. The present study targeted to elucidate the anti-cancer potential of resveratrol against the 7, 12-dimethylbenz[a]anthracene induced skin carcinogenesis in swiss albino mice. Intraperitoneal administration of resveratrol (5mg/kg and 10mg/kg of the body weight) revealed a significant reduction (p<0.001) in the tumor incidence, tumor burden and the mean tumor volume as compared to the control group. Also, towards the end of 10 and 22 weeks, resveratrol restored the activities of the antioxidant enzymes significantly in the treated groups. Histopathological studies revealed thickened corrugated and hyper-proliferative epidermis in skin tumor of 7, 12-dimethylbenz[a]anthracene induced mice and the similar results were found to be at significantly lesser extent post resveratrol treatment. The cumulative results of this study indicate that the resveratrol has potentials to modulate the 7, 12-dimethylbenz[a]anthracene induced histopathological and biochemical alterations during skin melanoma in mice.