Aim To observe the occurrence and the morphological manifestation of atherosclerotic lesions in apolipoprotein E gene knockout (ApoE -/-) mice. Explore the relationship between lesion formation and adventitial inflammation. Methods The successive sections of the hearts of 60 and 112 weeks old ApoE -/- mice were made, then stained by Movat method. Trailled all the trunks and intra-myocardial small branches of coronary arteries for finding the lesions, and analyzed the relationship between lesion distribution and adventitial inflammation. The aseptic adventitial inflammation of the femoral artery in C57BL/6 mice were duplicated, detected the expression of adhesive molecules. Results There were extending lesions in the trunks of coronary artery, which extended directly from the aorta. There were in situ lesions in the branches of the trunks (including intra-myocardial small branches). There were inflammatory cells aggregation at the adventitia with the lesions at the corresponding intima. The infiltrating area of inflammatory cells was much larger than the area of lesion at intima. Some positions with inflammatory infiltration in adventitia could be seen without lesion at corresponding intima. All the in situ lesions were arised within ventricular muscle, most of the large in situ lesions appeared in the left ventricular wall. ICAM-1, VCAM-1 and adhesion of white blood cells could be seen at the intima of femoral artery in the mice with experimental aseptic adventitial inflammation. Conclusions The adventitial inflammation is one of the predisposing factors for the formation of lesions within the coronary artery.