Context: Polygonum multiflorum is known as a medicinal plant. It has been used as a folk medicine which showed antioxidative property.Objective: Protective effects of the water extracts (w/v:1/10) from fresh P. multiflorum (WEP) on carbon tetrachloride (CCl4)-induced liver damage in rats were investigated.Materials and methods: CCl4 was used for inducing liver damage of SD rats, and WEP and emodin were fed for eight consecutive weeks.Results: We found that emodin levels in fresh WEP was higher than that in ripening WEP. Rats were administered WEP and emodin, the main active compound, for 56 consecutive days. WEP significantly lowered the serum levels of hepatic enzyme markers, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and reduced the generation of malonaldehyde. Treatment with WEP recovered glutathione S-transferase and catalase activity in rats as compared to treatment with CCl4 alone. In addition, serum tumor necrosis factor-alpha, an inflammatory marker, was found to decrease in rats treated with WEP. In histopathological evaluation, fatty degeneration and necrosis were found to be significantly decreased in the CCl4 plus WEP treatment group.Discussion and conclusion: WEP may be effective in attenuating liver damage by reducing lipid peroxidation as well as by positively modulating inflammation.