Abstract: AIM:To investigate the effect of insulin treatment on ventricular remodeling and cardiac functions after myocardial infarction (MI) and the underlying mechanism. METHODS: MI models were established by ligation of the left anterior descending coronary artery (LAD). Eighty male adult Sprague Dawley rats were randomly divided into five groups: sham (n=20), MI+saline (n=20), MI+insulin (n=20), MI+etanercept (n=10), and MI+etanercept+insulin (n=10). Serum and myocardial tumor necrosis factor-α (TNF-α) were measured at 1 week and 4 weeks after MI. Left ventricular (LV) fractional shortening (FS), ejection fraction (EF), LV end-diastolic diameter (LVEDD) and end-systolic diameter (LVESD) were measured with M-mode echocardiography. Catheters were inserted into the right carotid artery and then advanced into the LV to record the LV end-diastolic pressure (LVDP) and LV maximum rates of pressure development (±LV dp/dtmax). RESULTS: Myocardial TNF-α increased after MI and insulin administration significantly reduced myocardial TNF-α in post-MI rats (P<0.05, n=6). Moreover, EF, FS, LVDP and LVdp/dtmax increased and LVESD decreased in MI+insulin group compared with those in MI+saline group (all P<0.05, n=10). Compared with those in MI+etanercept group, EF, FS, LVDP and LVdp/dtmax increased and LVESD decreased in MI+insulin+etanercept group (all P<0.05, n=10). CONCLUSION: Insulin treatment alleviates left ventricular dilation and improves cardiac functions after MI in rats, but these effects may not be dependent on the inhibition of myocardial TNF-α.