Aim Based on the mTOR/ULK1 autophagy signaling pathway to discuss the mechanism of gypenoside improving aorta lipid deposition of ApoE－/－ mice. Methods 30 healthy ApoE－/－ mice were randomly divided into the model control group and the gypenoside group, and the simvastatin group, 10 mice in each group. 10 C57bL/6J mice were used as the normal control group. The model control group, the gypenoside group and the simvastatin group were fed with high-fat diet for 4 weeks. The gypenoside group and simvastatin group were treated with gypenoside 2.973 g/(kg·d) and simvastatin 2.275 mg/(kg·d) by gastrogavage for 8 weeks, respectively. The normal control group and the model control group were given by gastrogavage with the normal saline of the same volume. The formation of atherosclerotic plaque of the mice was detected by HE staining, and the blood lipid level was detected by the fully automatic biochemical analyser. The expressions of ULK1, Beclin1, LC3 and p-mTOR proteins were dectected by the Western blot.Results Compared with normal control group, in the model control group, TG, TC and LDLC were significantly increased (P＜0.05), HDLC was significantly decreased (P＜0.05), large atheromatous plaques could be seen in aortic canal, ULK1, Beclin1 and LC3 were significantly decreased (P＜0.01), p-mTOR was significantly increased (P＜0.01). Compared with the model control group, in the gypenoside group and the simvastatin group, TG, TC and LDLC were significantly decreased (P＜0.05), HDLC was significantly increased (P＜0.05), atheromatous plaques in aortic canal were significantly decreased, ULK1, Beclin1 and LC3 were significantly increased (P＜0.01), p-mTOR was significantly decreased (P＜0.01 or P＜0.05). Conclusion Gypenosides could relieve the formation of atherosclerotic plaques and prevent atherosclerosis possibly through regulating the autophagy.