OBJECTIVE To investigate the cardioprotective effects of morphine on ischemic reperfused rat heart in vitro and its mechanism. METHODS The isolated rat heart was perfused in a Langendorff apparatus. Infarct myocardium was determined by TTC. Coronary flow (CF), heart rate (HR), left ventricular pressure (LVP), the first derivative of ventricular pressure (LVP/dtmax) and infarct size after ischemia and reperfusion in rat heart given 0.3 micro mol/L morphine were observed. The effects of naloxone and glibenclamide on the cardioprotection of morphine were also measured. RESULTS After ischemia and reperfusion, CF, HR, LVP and LVP/dtmax of isolated rat hearts decreased significantly (P < 0.01). After morphine preconditioning, HR, LVP and LVP/dtmax increased (P < 0.01) and infarct size was reduced significantly (P < 0.01), while no significant change in CF (P > 0.05). The cardioprotective effects of morphine were abolished by naloxone or glibenclamide completely. CONCLUSIONS Morphine can reduce ischemia-reperfusion injuries in isolated rat heart. The cardioprotective effects of morphine are mediated by a local opioid receptor-K(ATP) channel linked mechanism in rat hearts.