Abstract: AIM:To investigate whether insulin treatment attenuates collagen remodeling of non-infarcted myocardium after myocardial infarction (MI) in rats. METHODS: MI models were produced by ligation of the anterior descending coronary artery. Thirty four adult male rats were randomized to receive one of the following treatments: sham (n=6), saline ［4 ml/(kg·h) i.v. injection beginning 20 min before ischemia and continuing for 2 h; n=14］ and insulin treatment (50 U/L, i.v. injection following the same routine and hypodermic injection of insulin ［0.5 U/ml, 1 ml/(kg·day)］ for 7 days after ischemia surgery; n=14). Parameters of echocardiogram were compared prior to and 1 and 4 weeks after operation. Hydroxyproline concentration was detected using immunochemistry. Collagen I and collagen III expressions were measured by Western blot. RESULTS: Insulin treatment significantly improved cardiac function as evidenced by increased left ventricular ejection fraction (LVEF) at 1 and 4 weeks after MI (P<0.05, P<0.01). Cardiac remodeling decreased post-MI as evidenced by reduced collagen content (P<0.05). Western blot showed that the ratios of myocardial collagen I/III of rats 1 and 4 weeks after MI were significantly higher than those in the sham group (P<0.05). Insulin treatment reduced the ratios of collagen I/III compared with those in saline hearts 1 week post-MI (P<0.05), whereas there were no differences in the ratios of collagen I/III 4 weeks post-MI. CONCLUSION: Insulin prevents heart remodeling in non-infarcted myocardium after MI by decreasing cardiac collagen I/III ratio.