Abstract: OBJECTIVE To determine whether the cardioprotection of ischemic postconditioning and heptanol against ischemia/reperfusion (I/R） is mediated by gap junction. METHODS The isolated perfused hearts of male rats were subjected to 30 min of regional ischemia followed by 120 min of reperfusion. The infarct size and the level of lactate dehydrogenase (LDH) in the coronary effluent were measured. The arrhythmia scores and conduction velocity of ventricular myocardium were measured in global ischemia model of rat heart subjected to 30 min of ischemia followed by 120 min of reperfusion. Gap junction uncoupler heptanol and opener antiarrhythmic peptide 10 (AAP10) were administrated at the beginning of reperfusion for 15 min, respectively. RESULTS In the Langendorff perfused rat heart model, ischemic postconditioning (3 cycles of 10 s reperfusion/10 s regional ischemia starting at the beginning of the reperfusion) and heptanol reduced infarct size and LDH release, ischemic postconditioning also improved the recovery of the left ventricular developed pressure, maximal rise/fall rate of left ventricular pressure and rate-pressure product (left ventricular developed pressure multiplied by heart rate). Ischemic postconditioning (6 cycles of 10 s reperfusion/10 s global ischemia starting at the beginning of the reperfusion) and heptanol reduced arrhythmia scores and conduction velocity of ventricular myocardium. Administration of AAP10 attenuated the cardioprotection of ischemic postconditioning and heptanol. CONCLUSION The cardioprotection of ischemic postconditioning and heptanol may be related to the attenuation of gap junction communication on myocardial ischemia/reperfusion injury.