Genetically modified hyperlipidemic mice provide important information on the pathogenesis of atherosclerosis, but most experimental designs are limited to in vitro or ex vivo examinations. The present study was designed to detect atherosclerotic lesions in situ in apolipoprotein E-knockout (apoE-KO) mice using a newly developed angiography system, synchrotron radiation (SR) microangiography, which uses monochromatic SR as an X-ray source and a high definition camera or video system as a detector. Digital microangiography with 7 mm pixel sizes was carried out and atherosclerotic lesion in small arteries less than 500 microm in diameter were detected. Moreover, the coronary artery stenotic lesion of an apoE-KO mouse was detected in situ with the angiography system. The new SR microangiography system is a powerful tool for investigating atherosclerotic lesions in situ in genetically engineered mice and will promote the basic study of atherosclerotic disease.