Objective To study the preventive effect of a Chinese traditional medicine, Huanglian Jiedu Decoction (HLJDT), on alcoholic fatty liver in mice, and provide experimental evidence for clinical prevention and treatment of alcoholic liver disease. Methods Sixty healthy SPF male C57 mice were randomly divided into control group, model group and low, medium and high dose HLJDT(0.61, 1.22, 2.44 g/kg/d)groups, 12 mice in each group. The mice of model groups were given gastric gavage of 50% ethanol, combined with concomitant HLJDT intervention for 6 weeks. The mice of control group received the same volume of saline. The body weight, liver index, serum biochemical indexes were determined and histopathological changes in the liver and colon tissues were examined and analyzed at 6 weeks after the experiment. Results Body weight gains of the mice in all the three dose HLJDT groups were significantly higher than that of the control group (P<0.05),liver index and the serum ALT, AST and TG contents were significantly decreased (P<0.05 for all). Histological changes in the liver of all the three dose HLJDT groups were significantly milder than those of the model control group, and also improving of the colon mucosal alterations was observed in the three dose HLJDT groups in a dose-dependent manner. Conclusions Huanglian Jiedu Decoction can well reduce the permeability of intestinal mucosa, and exerts certain preventive and protective effects on alcoholic liver injury in mice.