Abstract: AIM:To observe serum lipid and histopathological changes in ApoE gene knockout mice fed a normal diet instead of a high-fat diet. METHODS: Twenty eight-week-old mice (male) with ApoE gene knockout were selected and 20 C57BL/6J mice (male) were used as controls. The mice in both groups were fed normal diets for 6-8 months and the levels of TC, TG and LDLwere measured in the two groups. Routine aortic pathological productions were stained by HE to observe the pathological changes. RESULTS: Levels of TC, TG and LDL-c in mice with ApoE knockout gene were significantly higher than those in control group (P<0.05) and atherosclerotic plaques formed in ApoE gene knockout mice. CONCLUSION: ApoE gene knockout mice fed normal diets for 8 months are the ideal animal models for studies on atherosclerotic plaque research.