Background Ginseng, an ancient and famous medicinal herb in the Orient, has been used as a valuable tonic and for the treatment of various diseases including hepatic disorders. Ginseng extracts and individual ginsenosides have shown a wide array of beneficial role in the regulation of regular liver functions and the treatment of liver disorders. Objective: This study tries to determine the hepatoprotective , antioxidant and anti-inflammatory effects of ginseng on Methotrexate (MTX)-induced hepatotoxicity Materials and Methods: forty  rats (weigh 150-180 g) were used. The rats were kept in animal house for one week and had access to water and food  . Temperature was kept at 37 °C. After one week, the rats were randomly divided into four equal groups: Group (A) (control)  received normal saline ; group (B )received Ginseng(1.8 ml/kg/day) orally ; group( C) received MTX (100 μg/kg) intraperitoneally and group (D) received MTX (100 μg/kg) intraperitoneally with ginseng (1.8 ml/kg/day) orally. After six weeks, the rats were decapitated and  evaluation of liver function was done. Results: Ginseng treatment markedly suppressed the serum alanine aminotransferase (ALT) , aspartate aminotransferase (AST) and serum gama glutamil transpeptidase (λGTP)   activiteis  . Ginseng was attributed to stimulate anti-oxidant protein contents, such as glutathione peroxidase (GPX). The marked increase of proinflammatory cytokines ( TNF α )  in MTX treated rats  group was additionally attenuated by ginseng, Conclusion : Ginseng effectively prevent liver injury, mainly through down regulation of oxidative stress and inflammatory response.