Abstract: OBJECTIVE To observe the effects of hawthorn leaf flavonoids(HLF) on regulating lipid and protecting liver and the expression of HMG-CoA reductase(HMGCR) and low density lipoprotein receptor(LDLR) in hyperlipidemia mice. METHODS Fifty KM mice were randomly divided into the normal control group, model control group, low dose(1.5 g·kg^-1) and high dose(3.0 g·kg^-1) of HLF groups, simvastatin group. Except the normal control group fed basic food, the other groups were given high-fat diet. During the experiment, all mice free drunk water for 5 weeks. Animals were administered with corresponding drugs for 5 weeks. The blood was collected after the administration 2 weeks and 5 weeks respectively from the orbit to detect total cholesterol(TC), triglyceride(TG), high-density lipoprotein cholesterol(HDL-C), low density lipoprotein cholesterol(LDL-C), aspartate aminotransferase(AST) and alanine aminotransferase (ALT) levels. The liver was dissected after the last administration of blood sampling to observe the histopathological changes of the liver tissues by HE staining. The expression levels of HMGCR and LDLR in the liver tissues were detected by immunohistochemistry. RESULTS Compared with the normal control group, serum levels of TC, TG, LDL-C, ALT and AST were significantly increased while HDL-C level was decreased in the model control group whose the expression level of HMGCR was significantly increased in liver tissue after the modeling 5 weeks, and liver steatosis was severe. Meanwhile, the expression level of LDLR in liver tissue was significantly reduced in the model control group. Compared with the model group, serum levels of TC, TG, LDL-C, ALT and AST were significantly decreased while HDL-C level was increased in HLF 1.5 and 3.0 g·kg^-1 doses of groups whose the expression level of HMGCR was significantly reduced in liver tissue after the administratin of 5 weeks. Meanwhile, the expression level of LDLR in liver tissue was significantly increased in HLF group. The effect was more significant in 3.0 g·kg^-1 group than 1.5 g·kg^-1. The liver tissue in the model group showed fatty degeneration, while pathological changes of liver tissue were improved in HLF different doses of groups. CONCLUSION The HLF can reduce blood lipid level, improve liver function and reduce liver steatosis in hyperlipidemia model mice, which suggested that it has better function of regulating lipid and protecting liver. The mechanism might be related to the down-regulation of HMGCR expression to inhibit cholesterol biosynthesis and up-regulating of LDLR expression to promote cholesterol metabolism, which regulate lipid metabolism disorder.