Aim Previous studies performed in vitro indicated that XBP-01, a polypeptide which was refined from Chinese cobra venom (Naja naja atra), could inhibited the cultured vascular smooth muscle cell proliferation. To observe the eliminating atherosclerotic plaques effect of XBP-01 in vivo. Methods After fed with the atherogenic diets for 17 weeks, the atherosclerotic sensitive inbred strain C57BL/6J mice have typical atherosclerotic plaques formed near the aorta sinus, accompanied with the serum total cholesterol and triglyceride significant rise. Then the mice were injected with XBP-01 of 3.2 μg/g weight body per day for 4 weeks. Cryostat frozen sections, 10 μm thick, were cut from heart to aorta, stained with Red oil O. The sections were examined microscopically and scored according to the method of Roberts and Thompson. The serum total cholesterol and triglyceride also were assayed. Results The mice have typical atherosclerotic plaques formed near the aorta sinus, accompanied with the serum total cholesterol and triglyceride significant rise after fed with the atherogenic diets for 17 weeks. The plaques are fewer and less than that of the non-treating with XBP-01 group, the Roberts & Thompson score is 8.0±1.2, 4.1±2.2, respectively, and has a statistical significance. The serum total cholesterol and triglyceride descends to normal level. Conclusions XBP-01 possesses the potential antiatherosclerotic effect in vivo.