The protective effects of puerarin on liver damage were evaluated by carbon tetrachloride (CCl4)-induced hepatotoxicity in rats. Male rats were orally treated with puerarin daily, and received CCl4 intraperitoneally twice a week for 4 weeks. Our results showed that puerarin at doses of 50, 100, and 200 mg/kg b.w. significantly reduced the elevated activities of serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase at least 15%, 17%, 14% and 18%, respectively. In addition, puerarin at different doses significantly decreased (p < 0.05) the level of hepatic thiobarbituric acid reactive substances compared to the CCl4-treated group. Furthermore, the treatment of puerarin was also found to significantly increase the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase, and glutathione content at least 40%, 12%, 25%, 52%, 17% and 44% in the liver of CCl4-treated rats, respectively. Liver histopathology also showed that puerarin reduced the incidence of liver lesions induced by CCl4. The results suggest that puerarin exhibits potent hepatoprotective effects on CCl4-induced liver damages in rats, and that the hepatoprotective effects of puerarin may be due to both the inhibition of lipid peroxidation and to increase of antioxidant enzymes activity. (c) 2013 Elsevier Ltd. All rights reserved.