Investigations have shown that Rg3 can reverse the M1 polarization to the M2 phenotype in diabetic conditions to repress the occurrence of diabetes-complicated atherosclerosis (Guo et al., 2018), our further experiments confirmed that HFD for 12 weeks lead to plenty of atherosclerotic plaque formation in aorta of ApoE−/− mice, accompanied by abnormal lipoprotein profiles in serum, while Rg3 decreased LDL level and increased HDL level in serum of ApoE−/− mice, inhibited atherosclerotic plaque formation obviously. Here, APOE is linked to atherosclerosis.