The effects of streptozotocin (STZ)-induced diabetes (DM) and insulin on cardiac performance were investigated during reperfusion after low-flow ischemia in rats. Hearts were isolated 4 weeks after intravenous injection of STZ (65 mg/kg) or vehicle and retrogradely perfused in the presence (throughout the perfusion period) or absence of 1 U/L insulin using a Langendorff apparatus. Normothermic low-flow global ischemia was instituted by reducing the flow rate to 5% of baseline for 30 min, followed by reperfusion for 30 min. Rate pressure product (left ventricular developed pressure x heart rate) was calculated as an index of cardiac performance. Myocardial concentrations of adenine nucleotides, creatine phosphate (CP) and glycogen were measured. Insulin perfusion increased preischemic myocardial glycogen content in both DM and control hearts. Recovery of cardiac performance and myocardial CP concentrations in the absence of insulin was greater in the DM hearts than in controls during reperfusion. Insulin perfusion improved recovery of cardiac performance and elevated CP concentrations in both DM and control hearts. These results demonstrate greater cardioprotection against ischemia/reperfusion injury in the STZ-DM state and with insulin perfusion. These protective effects may be associated with augmented resynthesis of high-energy phosphates during reperfusion.