Objective To investigate the protective effect of propofol and/or fentanyl in myocardial ischemia-reperfusion injury. Methods Thirty-two SD rats weighing 250-300g were anesthetized with intraperitoneal ketamine 80 mg. Their hearts were excised and perfused with oxygenated (95%O2 and 5% CO2) K-H solution in a Langendorff apparatus at a perfusion pressure of 7.8 kPa. The temperature of perfusate and heart were kept at 37 ℃ . The experiment was divided randomly into four groups: A control group was perfused with K-H solution containing intralipid 90 ?g?kg-1 ( n = 8); B propofol group was perfused with K-H solution containing propofol 5?g?kg-1 ; C fentanyl group was perfused with K-H solution containing fentanyl 10 ng?kg-1; D propofol-fentanyl group was perfused with K-H solution containing propofol 5?g ?kg-1 and fentanyl 10 ng?kg-1. The isolated heart was perfused with above mentioned perfusate for 10 min followed by 50 min global normothermic (37℃) ischemia and 30 min reperfusion. The left ventricular developed pressure (LVDP) and ?dp/dtmax and coronary flow were measured 1 min before propofol and/or fentanyl perfusion, 1 min before global ischemia and at the end of 30 min reperfusion. The lactate dehydrogenase(LDH) activity in the total coronary effluent collected during the 30 min reperfusion was measured. Results The recovery of LVDP and ? dp/dtmax and coronary flow at the end of 30 min reperfusion were significantly better in group B, C and D than those in control group and the recovery was best in group D. The release of LDH in coronary effluent decreased significantly at the end of 30 min reperfusion in group B, C and D as compared with that in control group. LDH release was least in group D. Conclusions Both propofol and fentanyl can protect myocardium against ischemia- reperfusion injury in isolated rat hearts. The protective effect of propofol and fentanyl can be added and better protection can be provided.