In conclusion, our study initially revealed that Rg3 can ameliorate the healing and anti-monocyte adhesion ability of endothelial cells under high ox-LDL environment and alleviate atherosclerotic plaque induced by HFD in ApoE−/− mice, which are related to regulating the ICAM-1, VCAM-1 expression in HUVECs and vascular endothelium via PPARγ/FAK pathway, indicating that Rg3 has good protective effect on atherosclerosis caused by dyslipidemia and is related to its protective effect on endothelium. This evidence concerns the gene VCAM1 and metabolic syndrome.