Aim of this study: Graptopetalum paraguayense E. Walther, a vegetable consumed in Taiwan, has been used in folk medicine for protection against liver injury, although its actual efficacy remains uncertain. Therefore, we investigated the protective effects of Graptopetalum paraguayense E. Walther against carbon tetrachloride (CCl4)-induced liver damage in rats. Materials and methods: Water extracts of Graptopetalum paraguayense E. Walther (WGP) were administered for 8 consecutive weeks to male Sprague-Dawley rats. And a dose-dependent manner in preventing liver damage was confirmed. Moreover, the major ingredient of WGP, gallic acid, was also orally administrated in the CCl4-induced rats. The hepatoprotective activity was assessed using various biochemical parameters such as antioxidant enzymes and histopathological studies. Results: WGP ranging from 50 to 300 mg/kg bw administrations significantly lowered serum aspartate transaminase (AST) and alanine transaminase (ALT) levels, and inhibited malondialdehyde (MDA) generation in CCl4-treated rats. WGP increased cellular GSH level and antioxidant enzymes, including superoxide dismutase, glutathione reductase, and catalase. Serum tumor necrosis factor-alpha (TNF-alpha) was decreased in the group treated with CCl4 plus WGP (150 and 300 mg/kg bw). Histopathological examination of livers showed that WGP reduced fatty degeneration, cytoplasmic vacuolization and necrosis in CCl4-treated rats. In contrary, 10 mg/kg bw of gallic acid was administrated, this dose was related with WGP (300 mg/kg bw), and had significantly decreased the AST and ALT compared to the CCl4-treated group. Aforesaid results suggested that gallic acid from WGP offered antioxidative activity against CCl4-induced oxidative liver damage. Conclusions: Taken together, this study is the first time to suggest that Graptopetalum paraguayense E. Walther exerts hepatoprotection via promoting antioxidative and anti-inflammatory properties against CCl4-induced oxidative liver damage. (C) 2010 Elsevier Ireland Ltd. All rights reserved.