Valproic acid (VPA) is widely used worldwide for the treatment of epilepsy, migraine and as a mood stabilizer in some psychiatric diseases. It has been condemned for causing hepatotoxicity. Oxidative stress and some metabolites of VPA have been proposed to be responsible for VPA induced hepatotoxicity. The current study was conducted to assess the damage induced by toxic doses of valproic acid on rats' livers and to assess the protective role of silymarin and ascorbic acid in VPA induced hepatotoxicity. Forty-two male albino rats were divided equally into seven groups; group (1): normal control, group (2): ascorbic acid, group (3): silymarin, group (4): VPA, group (5): VPA+ascorbic acid, group (6): VPA + silymarin and group (7): VPA + ascorbic acid + silymarin. After four weeks, the animals were sacrificed and livers were collected for histopathologic examination and biochemical assessment. VPA group showed a significant increase in serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, bilirubin and a significant decrease in albumin and total protein. Liver malondialdehyde was significantly increased and antioxidant enzymes levels were significantly decreased. Liver sections showed loss of normal pattern of hepatocytes, inflammatory infiltration, congested central vein and fatty infiltration. Each of ascorbic acid and silymarin partially improved some of the measured parameters. When they were combined together, they depict high improvement in most of measured parameters and showed near normal liver sections. This study concludes that combination of ascorbic acid and silymarin has synergistic antioxidant and hepatoprotective effects against VPA induced toxic effects on liver.