It is widely believed that rupture of a vulnerable atherosclerotic plaque leads to acute coronary events and stroke. However, the exact mechanisms involved in the plaque rupture remain unknown. Pathological animal models are valuable in the research on human disease mechanism, their therapy, and drug development. Recently, we have proposed a novel murine model of atherosclerotic plaque rupture associated with not only intraplaque hemorrhage but also luminal thrombus using combination treatments of ligation and perivascular cuff placement on the carotid artery.