The present study was aimed to assess the effect of aqueous saffron extract (Crocus sativus L.) on sodium valporate (SVP) hepatotoxicity in albino rats. Treating rats with SVP induced many histological changes in the liver including cytoplasmic vacuolization of the hepatocytes, fatty degeneration and congestion of blood vessels. Biochemical results showed an increase in serum ALT and SAT. Moreover, SVP caused a reduction in total carbohydrates, total proteins and DNA in the hepatocytes. Animals treated with SVP and aqueous saffron extract revealed an improvement in the histological, histochemical and liver function enzymes,ALT and AST induced by SVP. These results indicated that saffron extract improved hepatotoxicity of SVP through inhibition of oxidative stress and enhancing the antioxidant defense system.