Objective To explore the effect of a herbalcompound Gehua Jiejue Dizhi Decoction (GJDD) on the liver fat deposition and the expression of PXR, and the mRNA and protein expression of its target genes CYP3A11 and CYP3A25in the liver tissues of mouse models of alcoholic fatty liver. Methods Twenty-nine healthy male C57BL/6J mice were randomly divided into control group (n=5), model group (n=8), high dose GJDD group (n=8)and low dose GJDD group (n=8). The mouse model of alcoholic fatty liver was prepared according to the National Institute on Alcohol Abuse and Alcoholism (NIAAA) method. Then, the mice were treated with the high dose and low dose GJDD for 9 days. Serum glutamic-pyruvic transaminase (AST) and aspartate aminotransferase (AST) were detected by enzyme-linked immunosorbent assay (ELISA). Liver fat deposition was detected by oil red O staining. Real-time RT-PCR and immunohistochemistry were performed to examine the expressions of PXR, CYP3A11 and CYP3A25. Results Compared with the model group, the liver fat deposition in the intervention groups was significantly reduced in a dose-dependent manner, with a significant increase of the expression of PXR and CYP3A25 (P< 0.01). The serum ALT level was significantly reduced in the model group (P< 0.01), while the transcriptional levels of CYP3A11 mRNA in the groups were similar (P ≥ 0.05). Conclusions Gehua Jiejue Dizhi Decoction has obvious therapeutic effect on the AFLD in mice, which may be related to the activation of PXR and its target genes CYP3A25.