Background and objectives: Ethanol exposure produces hypertension and many changes in the kidney. Melatonin has potent antioxidant and anti-inflammatory properties. The aim of this study is to detect the role of melatonin on arterial blood pressure (ABP) and its probable protective effects against renal dysfunction induced by ethanol in adult male rats. In addition, the possible involved mechanisms of melatonin using biochemical and histopathological methods were evaluated. Methods: Forty eight rats divided into three groups; control, ethanol treated and melatonin + ethanol treated groups. Half of the animals were sacrificed after six weeks (6Ws) and the other after twelve weeks (12Ws) for each group. Ethanol treated group: the animals of this group received 10 ml/kg of BW 30% ethanol by intra-gastric tube at alternate days. Melatonin+ ethanol treated group: the animals of this group received the pervious ethanol dose and 5 mg/kg melatonin injected subcutaneously at alternate days. Results: In ethanol treated group after the 6th and 12th week, there were significant decreased body weight (BW), significant increased (ABP) and tumor necrosis factor alpha (TNF-α). However, after the 6thW serum urea, creatinine, vascular endothelial growth factor (VEGF) and renal caspase-3 activity were not significantly changed, but these parameters were significantly increased except VEGF which significantly decreased at (12Ws). In ethanol treated group for 6Ws and 12Ws dilatation, congestion of the peritubular vessels and dilated bowman's spaces were obvious. Dilated tubules lined by thinner epithelium with degenerated cells at some areas were also noticed. Degeneration and necrosis of renal tubular epithelia were more obvious following twelve weeks ethanol treatment. These damaging changes reflected toxic effects of ethanol with the duration of exposure. These parameters and histopathological effects were ameliorated by the melatonin. Conclusion: Melatonin has a protective role in elevated (ABP) and renal damage induced by ethanol.