Objective To study the effects of atherosclerotic high-fat diet on body weight, blood glucose, blood lipid levels and atherosclerotic plaque formation in mice, and to determine the effect of fasting time on the results of blood lipid testing. Methods 10-week-old male ApoE knockout (ApoE^-/-) mice were given high-fat diet and normal diet. The atherosclerotic plaques were observed four months later. 10 week old C57BL/6J male mice were given regular diet for 4 weeks, regular diet for 2 weeks + high-fat diet for two or four weeks. Body weight、liver、glucose, and the serum lipid levels were examined. The influence of fasting for 12 h, 6 h or no fasting on blood lipid detection results before sacrificing were studied. Results The atherosclerotic plaque area of ApoE^-/- mice given high-fat diet increased significantly (P<0.01). C57BL/6J mice given high-fat diet gained weight (P<0.01). The glucose, TC, LDL-c and HDL-c were also increased in C57BL/6J mice with liver fat accumulation while the level of TG was significantly decreased(P<0.01). Compared with the fasting 12 h group, serum triglyceride (TG) was significantly increased (P<0.01）in fasting 6 h and no fasting groups. Conclusion The atherosclerotic high-fat diet can accelerate the formation of atherosclerotic plaques in ApoE^-/- mice, significantly increase blood sugar, TC and LDL-c levels, but significantly reduce TG values.. The fasting time can affect serum triglyceride (TG) level.