To evaluate the beneficial effects of Chinese bayberry (Myrica rubra Sieb. et Zucc.) flavonoid extract (CBFE) on chronic alcohol-induced liver oxidative injury in mice, experimental mice were pretreated with different doses of CBFE (50-200 mg/kg) for 4 weeks by gavage feeding. Biochemical markers and enzymatic antioxidants from serum, liver tissue, mitochondria and microsomes were examined. Our results showed that the activities of TC, TG, L-DLC in serum, the activity of CYP2E1 in microsomes, and the levels of MDA in liver tissue and mitochondria, decreased significantly (P < 0.05) in the CBFE-treated group compared with the alcohol group. On the contrary, the activities of ALT, AST, and H-DLC in serum, enzymatic antioxidants GSH-Px, SOD and GST in liver tissue and mitochondria, and HO-1 in microsomes rose markedly (P < 0.05). Histopathological examination revealed that CBFE (200 mg/kg) pretreatment noticeably prevented alcohol-induced hepatocyte apoptosis and fatty degeneration. It was suggested that the hepatoprotective effects exhibited by CBFE on alcohol-induced liver oxidative injury may be due to its potent antioxidant properties.