This study was planned to investigate the protective effect of L(+)-ascorbic acid (Vit C) on CCl4-induced hepatotoxicity and oxidative stress in the liver of Wistar rats (Rattus Norvegicus, strain Wistar). Twenty-four adult male Wistar rats were fed with standard rat chow diet for 10 days and randomly were divided into four groups of six each as follows: (1) control, (2) CCl4, (3) "CCl4 + Vit C", (4) Vit C groups. CCl4 was applied to rats belonging to CCl4 and "CCl4 + Vit C" groups Subcutaneously at 1 mg ka(-1) dose CCl4 for 3 days. Vit C applied to "CCl4 + Vit C" and "Vit C" group rats intraperitoneally at 300 mg kg(-1) dose for 3 days. All rats were sacrificed and livers were quickly removed on the fourth day of the experiment. MDA, total glutathione (T.GSH) levels and superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX) activities were measured in the liver of all groups of rats and also serum alanine amino transferase (ALT) and aspartate amino transferase (AST) activities were detected to determine liver functions in all groups of rats. Histopathological changes were evaluated by light and transmission electron microscopes. In "CCl4 + Vit C" group, MDA level was significantly decreased (p < 0.05) and SOD, CAT, GSH-PX activities were significantly increased (p < 0.005, 0.01, 0.05) respectively, T.GSH level was significantly increased (p < 0.005) and serum ALT and AST activities were significantly decreased (p < 0.01, 0.05), respectively, when compared with CCl4 group. These results show that Vit C has a highly protective effect on hepatotoxicity and oxidative stress caused by CCl4. Copyright (C) 2009 John Wiley & Sons, Ltd.