Thirty male BALB/c mice were randomly divided into five groups (n=6). Group A received 0.2 ml normal saline intraperitoneally served as control for MTX. Group B received 0.2 ml distilled water orally for 7 days served as control for oral silymarin. Group C received single intraperitoneal injection of MTX 20 mg/kg. Group D received silymarin 25 mg/kg orally for seven days. Group E received silymarin 25 mg/kg orally for 7 days with MTX 20 mg/kg intraperitoneally at day 4. Blood samples for measuring serum ALT (Alanine Transaminase), AST (Aspartate transaminase) and ALP (Alkaline Phosphatase) along with liver samples for hepatic histological examination were taken after 24 hours of last dose. Results: Silymarin show hepatoprotective effect against MTX induced hepatotoxicity. Conclusion: Silymarin has hepatoprotective potential when administered along with MTX. Key words:Hepatoprotective, Hepatotoxicity, Methotrexate, Silymarin.