To evaluate the Renoprotective efficacy of melatonin against long term exposure induced changes of dimethylbenz(a)anthracene (DMBA), cell proliferation and DNA synthesis was determined in the epithelial cells of cortical and medullary renal tubules in female and male mice applying quantitative autoradiographic analysis and using 3H thymidine as a radioactive label. A total of 30 male and female adult albino mice were divided into 3 groups, each of 10 individuals: control (group C), DMBA exposed (group D) and DMBA/melatonin exposed (group D+M) mice. In female mice, long term exposure for 150 days to a single injection of DMBA (10mg/ 100g b.w.) stimulated the incorporation rate of 3H thymidine into the epithelium of cortical renal tubules by 6774% compared to control. The number of grains over labeled nuclei was reduced by 57.1%. Daily injected with melatonin (100 g/ 100g b.w.) during the last 60 days of exposure to a single dose of DMBA attenuated cell division rate of the epithelial cells by 80% compared to group D, but remained 1275% higher than that of group C. The mean grain count over labeled nuclei was increased by 59.5% compared to group D, but remained 31.5% lower than that of control. In medullary portion of the renal tubules, DMBA induced changes were less pronounced than that in the cortical area. The cell division was stimulated by 833% compared to control and remained 8.1x lower than the percentage increase in the cortical part. The mean grain count over labeled nuclei was reduced by 40.4% compared to group C. Daily injected with melatonin (100 g/ 100g b.w.) during the last 60 days of exposure to a single dose of DMBA reduced the mitotic cell division by 83.9% compared to group D and thereby showing a similar effect as in the cortical part of the renal tubules. Compared to group C, the 3H labeling index remained 50% higher. In the cortical portion, the comparable value was 1275% higher than that of control. The mean grain count over labeled nuclei was increased by 26.2% compared to group D and remained 24.8% lower than in group C.