Fisetin (3, 7, 3′, 4′-TetrahydroxyFlavone) is a bioflavonoid found in fruits and vegetables. It displays a wide variety of pharmacological properties, including antioxidant, anti-carcinogenic and anti-inflammatory effects. This study was done to explore the role of fisetin, in ameliorating oxidative damage in thioacetamide (TAA)-induced hepatic injury in rats. Thirty-six male albino rats were divided into three equal groups. Group I (normal control group): rats administered distilled water only. Group II (TAA-intoxicated group): rats received thioacetamide (50 mg/kg b. wt.) intraperitoneally twice weekly for 6 weeks. Group III (TAA + fisetin co-treated group): rats received thioacetamide (50 mg/kg b. wt.) and at the same time administered fisetin (10mg/ kg b. wt. /daily /orally) for 6 weeks (end of experiment). All animals were sacrificed after 6 weeks. The results revealed that serum levels of Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) were significantly elevated in Group II. Oxidative stress in the group II was manifested by a significant rise in Malondialdehyde (L-MDA) levels with a marked reduction in Glutathione (GSH) content and diminished activity of antioxidant enzyme Glutathione-S-Transferase (GST), in liver tissues as compared with the control group. The coadministration of fisetin and thioacetamide (protection modality) restored the thioacetamide induced alterations in liver functions, promoted oxidative stress and antioxidant defense. Thus, the results of the present study indicate that fisetin treatment protects the hepatocytes by improving the antioxidant competence in hepatic tissues of thioacetamide intoxicated rats.