〔Abstract〕 Objective To investigate the therapeutic effect and mechanism of isoliquiritigenin(ISL) on hepatic fibrosis(HF). Methods SD rats were randomly divided into normal group, model group, colchicine tablet group(positive control, 0.1 mg/kg), and high-dose and low-dose ISL groups(40, 10 mg/kg).Except for the normal group, the other groups were given intraperitoneal injection of 50% carbon tetrachloride(CCl4) olive oil solution(1.5 ml/kg) to establish liver fibrosis models, twice a week for 8 weeks. After modeling, rats in each group were given the corresponding drugs by gavage at a volume of 10 ml/kg per day for 4 weeks.After the last administration, the levels of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) in the serum of rats were determined; liver index was calculated; HE and Masson staining were used to observe the pathological changes of liver tissue; Real-time quantitative PCR was used to detect the mRNA expression levels of hypoxia-inducible factor-1α(HIF-1α) and vascular endothelial growth factor(VEGF); the expressions of HIF-1α and VEGF protein in liver tissue were detected by immunohistochemistry and Western blot. Results Compared with the normal group, the serum ALT and AST contents of the rats in the model group increased(P<0.01), the liver index increased(P<0.01), the rat fibrous tissue hyperplasia, the collagen volume fraction increased(P<0.01), and the liver the expression levels ofHIF-1αandVEGFmRNA in the tissue increased(P<0.01). Immunohistochemistry and Western blot showed that the expression levels of HIF-1α and VEGF protein increased in the model group(P<0.01). Compared with the model group, the ISL high and low dose groups could reduce the levels of ALT and AST in serum(P<0.01), the liver index(P<0.01), the proliferation of fibrotic tissue and the collagen volume fraction(P<0.05), down-regulate the expression levels ofHIF-1αandVEGFgenes(P<0.01). Immunohistochemical detection showed that the high and low dose groups of ISL could reduce the protein expression levels of HIF-1α(P<0.01,P<0.05),the expression level of VEGF protein decreased(P<0.01), Western blot detection showed that the high-dose group of ISL could reduce the protein expression levels of HIF-1α and VEGF(P<0.05). Conclusion ISL has a significant therapeutic effect on CCl4-induced HF model rats, and its mechanism may be related to the regulation of HIF-1α and VEGF protein expression levels.