Abstract: AIM: To study the cardioprotective effect uridine triphosphate (UTP) on ischemia/reperfusion injuries of rat hearts and to explore whether this effect of UTP is mediated by P2Y receptor. METHODS: Twenty-four Sprague Dawley (SD) rats were divided into four groups: control group (0.9% sodium chloride i.v.), UTP group (4.4 μg/kg i.v.), UTP and suramin (antagonist of P2Y receptor) group (4.4 μg/kg i.v.+30 μg/kg i.v.) and suramin group (30 μg/kg i.v.). Twenty-four h after drug injection, rat hearts were isolated and perfused with K-H solution by Langendorff system. The hearts were subjected to 25 min ischemia followed by 40 min reperfusion. Hemodynamic indexes were measured and ECG was recorded. The coronary effluent was collected to measure the lactate dehydrogenase (LDH) level. Ultrastructure of myocardium was observed by transmission electron microscope. RESULTS: Twenty-five min after ischemia, significantly better recovery percentage of left ventricular function (P<0.05, P<0.01) and lower LDH level and arrhythmia incidence rate (both P<0.01) were observed in UTP group compared with those in control group. The myocardial ultrastructure of the UTP group was generally normal and the cardioprotective effects of UTP were eliminated by suramin. CONCLUSION: UTP pretreatment protects rat hearts from ischemia/reperfusion injury, which is cancelled by P2Y receptors’ antagonist suramin, indicating that the myocardial protective effect of UTP is mediated by P2Y receptors.