Introduction: Liver fibrosis represent a worldwide challenge of clinical importance, results from  chronic damage of liver, and evidenced by build up of excessive extracellular matrix proteins.. The present study was carried out to evaluate the antifibrogenic effect of grape seed extract (GSE) against hepatic fibrosis induced by CCl4 in mice. Experimental Design: forty adult male albino mice were divided into four equal groups; first (control) in which mice were injected IP with olive oil as vehicle. In the second group  (GSE) mice were received GSE orally at a dose of 200mg/kg/day for 8 weeks while in the third group (CCl4) mice were injected IP with  CCl4 (0.4ml/kg / twice weekly) for 8 weeks . In the fourth (GSE+ CCl4) group mice were injected IP with CCl4 and co-treated with GSE orally as in previous treated-groups. At the end of the experiment, animals were sacrificed and blood samples and liver tissue specimens were collected. Results: the examined liver of CCl4-intoxicated group revealed marked hepatic fibrotic lesions confirmed by Masson's trichrome stain and associated with the presence of intensely stained α -SMA-positive hepatic stellate cells (HSCs) in entire of the hepatic lobules and in the vicinity of bridging fibrotic septa. Hepatic degeneration and necrosis were also seen. This hepatic damage was associated with significant increases in AST and ALT activities with low albumin levels and hypoproteinemia. Co-administration of GSE with CCl4 improved the microscopic picture of liver where scanty fibrotic lesions and mild degeneration of some hepatic cells were recorded. Less intensely stain ed α -SMA-immunopositive cells were observed. Serum AST , ALT, albumin and total protein values were more or less within the ranges of these parameters in the control non-intoxicated group. Conclusion: GSE has potent antifibrogenic effect on CCl4-induced hepatic fibrosis by inhibiting HSCs activation, decreasing collagen synthesis and improving hepatic regenerative capability through its powerful antioxidant and anti-inflammatory properties.