OBJECTIVE： To study protective effect of grape seed proanthocyanidins （GSPE） against acute liver injury in mice and its mechanism. METHODS： 24 mice were randomly divided into normal group （normal saline）， model group （normal saline）， GSPE low-dose and high-dose groups （100， 200 mg/kg）. They were given relevant medicine intragastrically for consecutive 4 days， once a day. After the last administration， those groups were given vegetable oil solution containing 0.2％ CCl4 intraperitoneally to induce liver injury model except normal group； after modeling， those groups continued intragastric administration of medicine for 3 d. The effects of GSPE on liver appearance， pathological and liver coefficient in mice with acute liver injury were observed； the activity of ALT and AST were detected in serum； the expression of apoptosis-related protein Bcl-2 and Bax， that of autophagy-related protein p62 were detected in liver tissue； the expression of PCNA protein in liver tissue was determined. RESULTS： Compared with normal group， liver coefficient， the activity of ALT and AST in serum increased in model group； mice liver tissue pathological changes mostly concentrated in the grade Ⅲ； the expression of Bcl-2 and p62 protein were significantly lowered in liver tissue， while Bax expression was increased， the Bcl-2/Bax was decreased （P＜0.05 or P＜0.01）， the expression of PCNA protein was decreased in liver tissue. Compared with model group， liver volume， necrosis of liver cells and inflammatory cell infiltration decreased significantly， and lesion degree （concentrated in the grade Ⅰ and Ⅱ） and liver coefficient decreased； the activity of ALT and AST in serum decreased； the expression of Bcl-2， p62 and Bcl-2/Bax increased， while protein expression of Bax decreased （P＜0.05 or P＜0.01）， the expression of PCNA protein increased in liver tissue. CONCLUSIONS： GSPE exerts a protective effect on CCl4 induced oxidative liver injury in mice， and its mechanism may be related to promoting the proliferation of liver cell， inhibiting the apoptosis and autophagy of liver cells.