Aim To observe the Xue Zhi Kang’s (XZK) effect on blood lipid and atherosclerosis (As) of apolipoprotein E deficient (Apo E°)mice. Methods Six week old Apo E° mice were assigned randomly into hyperlipidemia group (fed with saline) and XZK group (fed with XZK). Six week old heathy mice (C57BL/6J mice) were the normal group (fed with saline ). They were treated for 14 weeks, then total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDLC) and high density lipoprotein cholesterol (HDLC) were determined, and the aortas were preceded in the formalin for morphological research and photograph analysis. Results TC, TG and LDLC of hyperlipidemia group were significantly higher than those of the normal group; TC, TG and LDLC of XZK group were definitely lower than those of hyperlipidemia group (p<0.05 ). The photography analysis showed that the lesion of hyperlipidemia group was very obvious. Compared with normal group, the total atheromatous plaque square increased obviously (p<0.05 ). Morphological reseach showed that As lesions were found in aortas of hyperlipidemia group and XZK group. While As lesions of hyperlipidemia group were more serious than those of XZK group, and no As lesions were found in normal group. Conclusion Xue Zhi Kang can lower the serum cholesterol and relieve the As lesions of the Apo E° mice.