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The present study was carried out to evaluate the hepatic changes, and antioxidant levels after using the methotrexate and investigate the protective and curative effect of resveratrol against these effects. This study was performed by determined the evaluate the liver function (AST,ALT,ALP and bilirubin) and antioxidant levels (catalase, GSH) and MDA. Twenty eight male rats were randomly divided into four equal groups. First group (Control) received distilled water only, second group treated with methotrexate (0.45 mg/kg.Bwt), third group treated with resveratrol (40 mg/kg.Bwt) 2 hrs before methotrexate (0.45 mg/kg.Bwt).fourth group treated with resveratrol (40 mg/kg.Bwt) 2 hrs after methotrexate (0.45 mg/kg.Bwt). The drugs were administrated orally for 28 days. The results showed that the animals that treated with methotrexate were suffered from liver damages by significant increasing in the liver enzymes and bilirubin and also, significant decreasing in the antioxidants (catalase and GSH), and significant increasing in the MDA.While resveratrol (before and after) methotrexate showed decreasing in the level of liver enzyme (ALT, AST and ALP) as compared with methotrexate alone. The administration of reseveratrol (before and after) methotrexate administration led to decrease in the levels of bilirubin as compared with methotrexate alone and significant increasing in the antioxidant parameters (catalase and GSH), while there were significant decreasing in MDA. In this study methotrexate induced alteration in the liver function and decreased the antioxidants levels, while the resveratrol have the ability to maintain liver function, and to increase antioxidant levels.