Abstract: Glutathione plays an important role in the detoxification of most toxic agents. This study was planned to investigate the protective effect of vitamin C on chronic and acute models of carbon tetrachloride (CCl4)-induced oxidative stress and changes of the glutathione concentration (GSH) in the liver and kidney of Wistar rats. The administration of vitamin C (Vit. C) to the rats (100 mg/1 kg) with intraperitoneal injection of CCl4 at dose level of 0.2 mL kg-1 (twice a week for 3 months) or 1 mL kg-1 (single dose) significantly reduced the elevated plasma levels of aminotransferases, alkaline phosphatase, blood hydroperoxide, malondialdehyde in liver and kidney and blood creatinine. Vit. C antagonized the decrease of GSH level caused by CCl4. In CCl4 (chronic dose) + Vit. C group, plasma cholesterol and triglycerides levels were significantly decreased, while high density lipoprotein and protein concentrations were significantly increased, when compared to CCl4 group. The treatment of rats with CCl4 as a single dose (1 mL kg-1) has no significant influence on lipids. Plasma urea and uric acid levels of CCl4+Vit. C group were significantly increased as compared to CCl4 group. These results showed that vitamin C had a protective effect on hepatotoxicity and renal toxicity caused by CCl4 induced oxidative stress via its antioxidative property, reducing the lipid peroxidation and normalizing the glutathione level with improved the alterations in the biochemical markers. Moreover, Vit. C showed hypolipidemic effect in CCl4-treated rats.