Aim To study the protecting effect of Polygoni Multiflori total glycosides(PMTG)on the atherosclerotic lesion formation. Methods Thirty-two female apolipoprotein E gene deficiency mice were randomized into four groups: PMTG high dose group [150 mg/(kg·d)],low dose group [25 mg/(kg·d)],atorvastatin positive control group [5 mg/(kg·d)],and blank control group. At the end of the tenth week, all mice were killed. The serum levels of total cholesterol (TC), Triglyceride (TG), high density lipoprotein cholesterol (HDLC)were measured by enzyme dynamics method. Light microscopy were adopted to assess the degree of As lesions of aortic wall and image analysis was performed with computer. Results As compared with the blank control group, 1.PMTG could reduce the levels of serum TC, TG significantly (TC: 649.3±72.2 mg/dL, 632.6±55.1 mg/dL, 497.4±140.8 mg/dL vs 809.4±42.6 mg/dL, respectively, p<0.01; TG: 126.6±48.1 mg/dL, 145.6±37.9 mg/dL, 172.1±15.7 mg/dL vs 253.3±42.6 mg/dL, respectively, p<0.01); but elevate HDLC level significantly(117.1±14.9 mg/dL, 113.5±23.3 mg/dL, 126.7±12.8 mg/dL vs 67.3±10.6 mg/dL, respectively, p<0.01). There are no differences beween cured groups in the serum level of blood lipids (p>0.05). 2.It could also reduce the extent of atherosclerotic lesion and the aorta plaque areas were significantly lower (3.97%±0.62%, 3.11%±0.01%, 0.86%±0.07% vs 18.50%±6.54%, respectively, p<0.05). Conclusion The resulting data provide the occurrence and the development of atherosclerotic lesions could be inhibited by the PMTG because of its lipid-regulated ability.