Objective To establish a stable mouse model of chronic myocardial ischemia in coronary artery disease and preliminarily elucidate the electrophysiological mechanisms of T-wave flattening under ischemic conditions. Methods APOE^{- / -} mice were randomly divided into a model group and a lipid-lowering drug (LLD) group and subjected to a high-fat diet for 3 months. C57BL/ 6J mice fed a normal diet were used as the control group. Electrocardiograms were used to assess the mice before and after modeling, and cardiac perfusion was evaluated via nuclear PET/ CT scans.Hematoxylin-eosin and oil red O staining were employed to assess pathological atherosclerosis (AS) plaque formation.Mouse myocardial cells were isolated, and action potentials were recorded. Results After modeling, mice in the model group exhibited a significant increase in cholesterol ( CHO) and low-density lipoprotein C ( LDL-C), along with the appearance of lipid plaques in the aorta. Lesions in the LLD group were noticeably reduced, and no plaques formed in the control group. Myocardial nuclear scans revealed impaired blood perfusion in the hearts of the model group mice that was significantly lower than that in the LLD and control groups. The electrocardiograms indicated a significant reduction in T/QRS in both the model and LLD groups, with no significant changes observed in the control group. Myocardial cell action potential recordings revealed an accelerated repolarization rate in the inner-layer myocardial cells under ischemia, and a reduction in the inner-to-outer potential difference was identified as the primary electrophysiological mechanism underlying T-wave flattening. Conclusions APOE^{- / -} mice can be used to establish a model of chronic myocardial ischemia. The increased repolarization rate of inner-layer myocardial cells is likely to be the main cause of T-wave flattening in electrocardiograms under ischemic conditions.