Abstract: AIM To investigate whether insulin (Ins) protects heart against ischemia/reperfusion (I/R) injury through stimulation of glucose metabolism. METHODS Fifty-four rats were randomly divided into three groups: glucose group (Glu), pyruvate group (Pyr) and palmitate group (PA), each group was randomly divided into Control group, I/R group, I/R+Ins group, six rats in each group. Hearts were subjected to 30 min of myocardial ischemia and 1 h of reperfusion and insulin was intravenously infused at 100 U/L for 1 h, 30 min before ischemia in vitro. Hemodynamic parameters (LVDP, ±dP/dtmax and CF) were detected by multi-channel physiology recorder, phosphorylation and total levels of Akt were determined by Western blot and cardiac infarct size was evaluated by staining with TTC. RESULTS Compared with those in control, LVDP, ±dP/dtmax and CF decreased in Glu, Pyr and PA groups following I/R (P<0. 01). After insulin treatment, LVDP, ±dP/dtmax and CF increased in Glu and Pyr groups (P<0. 05), but LVDP, ±dP/dtmax and CF did not change in PA group compared with those in I/R. Infarct size did not change in Glu, Pyr and PA groups compared with that in I/R, infarct size decreased in Glu and Pyr groups (P<0. 01), whereas infarct size in PA group did not decrease after insulin treatment. Western blot showed no obvious difference in t-Akt and p-Akt (Ser473) levels between Glu, Pyr and PA groups. Compared with those in I/R, up-regulated p-Akt (Ser473) was found in Glu, Pyr and PA groups (P<0.05). Glu group showed a further up-regulated p-Akt (Ser473) (P<0.05), whereas p-Akt (Ser473) level was not significantly different between Pyr group and PA group after insulin treatment. CONCLUSION Insulin protects heart against acute myocardial I/R injury through stimulation of glucose metabolism, which validates the concept that stimulating of glucose metabolism is a novel therapy for ischemic heart disease.Low HDL-C is associated with the risk CHD in Chinese Han population.