Aim To study the development of spontaneous atherosclerosis in combined hyperlipidemic mice. Methods Comparison of apolipoprotein (Apo) E/lipoprotein lipase (LPL)-double deficient mice with ApoE-deficient mice on the plasma triglyceride (TG),total cholesterol (TC), high density lipoprotein (HDL) as well as the atherosclerotic lesion area of the aortic root and the whole aorta. Results ApoE/LPL-double deficient mice had an approximately 60% and 380% increase in total cholesterol (7.237±0.448 and 4.435±1.892 g/L)and triglyceride (5.904±0.505 and 1.536±0.860 g/L)respectively, but high density lipoprotein was not significantly different from ApoE deficient mice. The atherosclerotic lesion area of the aortic root and the whole aorta were also not significantly different between the 2 groups of mice. Conclusion ApoE/LPL-double deficient mice display significantly higher plasma TG and Ch levels than ApoE deficient mice but the spontenous atherosclerotic lesions are not different.