Proanthocyanidins are naturally occurring compounds widely available in fruits, vegetables, nuts and seeds. They are a class of phenolic compounds and have been reported to exhibit a wide range of biological effects. In this study, we investigated the protective effect of grape seed proanthocyanidins on hepatic injury induced by dimethylnitrosamine (DMN) in rats. Treatment with DMN caused a significant increase in levels of serum alanine transaminase, aspartate transaminase, alkaline phosphatase, and bilirubin. Oral administration of proanthocyanidins (20 mg/kg daily for 4 weeks) remarkably prevented these elevations. Proanthocyanidins also restored serum albumin and total protein levels, and reduced the hepatic level of malondialdehyde. Furthermore, DMN-induced collagen accumulation, as estimated by histological analysis of liver tissue stained with Sirius red, was reduced in the proanthocyanidins-treated rats. A reduction in hepatic stellate cell activation, as assessed by ${alpha}$-smooth muscle actin staining, was associated with proanthocyanidins treatment. In conclusion, these results demonstrate that proanthocyanidins exhibited in vivo hepatoprotective and anti-fibrogenic effects against DMN-induced liver injury. It suggests that grape seed proanthocyanidins may be useful in preventing the development of hepatic fibrosis.