Objective:To explore the inhibiting effects and mechanisms of notoginsenoside R1 on liver lipid deposition in ApoE knocked out (ApoE-/-) mice. MethodsThe wild type C57BL/6J mice were taken as the normal group. The ApoE-/- mice were randomly divided into the model group and notoginsenoside R1 group. The normal group and the model group were treated with the solvent therapy, and the notoginsenoside R1 group was treated with notoginsenoside R1 at dose of 25 μg/g by intraperitoneal injection, with a course of 8 weeks. The changes on the liver pathological morphology and lipid deposition were observed after hematoxylin and eosin (HE) staining and oil red O staining. The total RNA was extracted from the liver. The gene expressions of PPARγ, LXRα, ABCA1, SRBI and the expressions of miR-26a, miR-33 and miR-122 were analyzed by Real-time PCR.  Results:The results of HE staining and oil red O staining revealed that compared with the normal control group, large vacuolation and degenerative hepatocytes swelling were observed in the liver tissues of mice in the model group, as well as a great number of lipid vacuoles and lipid deposition. Compared with the model group, the hepatocytes swelling was significantly relieved and the lipid vacuoles and lipid deposition were reduced in the notoginsenoside R1 group. The results of expression analysis on lipid metabolism-related genes and miRNAs revealed that compared with the model group, the expression levels of PPARγ, LXRα, ABCA1 and SRBI were significantly up-regulated in the notoginsenoside R1 group (P＜0.05, P＜0.01), and the expression level of miR-26a was significantly down-regulated (P＜0.05).  Conclusion:Notoginsenoside R1 can significantly suppress the liver lipid deposition in ApoE-/- mice, and its mechanisms may be associated with regulation on cholesterol metabolism.