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The liver has long been identified as a target organ of arsenic exposure. Arsenic is a potent environmental toxicant and its accumulation in the liver causes hepatotoxicity. In our study, the investigation of effects of melatonin on arsenic-induced liver damage in rats was planned. In our study, 27 male rats were divided into three groups: control (saline, 5 ml/kg/day, intragastrically), arsenic (sodium arsenite, 5 mg/kg/day, intragastrically), and arsenic+melatonin (sodium arsenite, 5 mg/kg/day, intragastrically and melatonin, 25 mg/kg/day, intraperitoneally) group. At the end of 15 days, the rats were weighed and sacrificed then liver tissues were collected. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidise (GSH-Px) activities as well as malondialdehyde (MDA) levels were determined by spectrophotometry. The amount of arsenic in liver tissue was analyzed by Inductively Coupled Plasma/Optical Emission Spectrometer (ICP-OES). There were no significant differences in respect to weights of rats among the groups. Arsenic significantly decreased the enzyme activities of SOD, CAT, and GSH-Px as well as increased the levels of MDA in liver tissues. Melatonin treatments significantly increased of reduced SOD, CAT, and GSH-Px enzyme activities and decreased the elevated tissue MDA levels in liver tissues. The amount of arsenic in liver tissues significantly increased in arsenic group. There were no significant differences in respect to the amount of arsenic in liver tissues between the arsenic group and melatonin group. These data suggested that melatonin has beneficial effects against arsenic-induced liver damage by decreasing oxidative stress and lipid peroxidation. [ABSTRACT FROM AUTHOR]