Coronary reperfusion improves ventricular function and survival after infarction, but the metabolic conditions at this time may not be optimal to protect the heart. The objective of this study was to evaluate if metabolic support with glucose-insulin-potassium (GIK) administered at the time of coronary reperfusion could elicit the same cardioprotection as GIK infusion during the entire ischemia/reperfusion period. Three groups of anesthetized, open-chest rats were subjected to 30 minutes of regional ischemia and 180 minutes of reperfusion. Groups 1 (controls) and 2 (GIK_IR) received saline or GIK, respectively, throughout the whole experimental period, whereas a third group (GIK_R) received GIK from the onset of reperfusion only. Infarct size was significantly reduced in the GIK-treated groups, compared with controls (GIK_IR 44 ± 5% and GIK_R 45 ± 5% vs. control 66 ± 4%; P < 0.05). Postischemic recovery of cardiac function improved when GIK was only administered during the reperfusion phase. Furthermore, infusion of GIK resulted in reduced plasma concentrations of free fatty acids and increased plasma glucose (both P < 0.05) compared with controls. This study demonstrates that glucose-insulin-potassium administration at the onset of the postischemic reperfusion period is as cardioprotective as administration of GIK during the entire ischemia/reperfusion period.