Abstract: Objective: To study the preventive effects of American ginseng and Hovenia dulcis Thunb (AGH) on alcohol-induced acute liver injury in mice. Methods: After one week of adaptation, ICR mice were randomly divided into normal group, model group and AGH (Ⅰ,Ⅱ,Ⅲ) groups. After giving the mice a continuous intragastric administration of AGH (100 mg/kg∙bw) for 14 days, all groups except the normal group were given three times of alcohol (5 g/kg) within 24 hours to induce liver damage. After the third alcohol administration for 6 hours, the mice were sacrificed. The activities of Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) and the content of Triglycerides (TG) in serum were tested. The activity of Glutathione peroxidase (GSH-Px), Superoxide dismutase (SOD) and the contents of Glutathione (GSH) and Malondialdehyde (MDA) were detected. Pathological changes of liver were observed by H & E staining. The expression of p-ERK, p-JNK and p-P38 protein in liver tissue was detected by WB method. Results: Compared with model group, AGH could significantly reduce the activities of AST and ALT in serum (P<0.05), decreased the level of TG in serum (P<0.05) and MDA content in liver tissue (P<0.01). Meanwhile, AGH could also increase the activities of SOD and GSH-Px in liver tissue (P<0.01) and improve the level of GSH in liver tissue (P<0.01). Pathological observation showed that the main degeneration was fat drops, and some inflammatory cells were infiltrated in model group. AGH group had different degree of improvement on the pathological changes of the liver in mice. AGH significantly inhibited the expression of p-ERK, p-JNK and p-P38 (P<0.01) and inhibited the apoptosis of hepatocytes. Conclusion: AGH has obvious protective effect on acute alcohol-induced liver injury in mice.