Objective To compare the effects of oxycodone and morphine on myocardial ischemia-reperfusion (I/R) injury in rats. Methods Forty-eight SPF healthy adult male Sprague-Dawley rats, aged 8-10 weeks, weighing 250-300 g, were randomized into 4 groups (n=12 each) using a random number table: sham operation group (S group), myocardial I/R injury group (I/R group), morphine group (M group) and oxycodone group (O group). Myocardial I/R was produced by occlusion of the anterior descending branch of the left coronary artery for 30 min followed by 120 min of reperfusion.In group S, the anterior descending branch of the left coronary artery was only exposed but not ligated.In M and O groups, morphine 1.5 mg/kg and oxycodone 0.5 mg/kg were injected, respectively, via the internal jugular vein at 5 min before ischemia.At the end of reperfusion, arterial blood samples were collected via cardiac puncture for determination of the serum creatine kinase-MB (CK-MB) and cardiac troponin I (cTnI) concentrations.Myocardial infarct size was measured by 2, 3, 5-triphenyltetrazolium chloride staining.Apoptosis in cardiomyocytes was determined by TUNEL, and apoptosis index (AI) was calculated. Results Compared with S group, serum CK-MB and cTnI concentrations and AI were significantly increased, and myocardial infarct size was enlarged in I/R, M and O groups (P<0.05). Compared with I/R group, serum CK-MB and cTnI concentrations and AI were significantly decreased, and myocardial infarct size was decreased in M and O groups (P<0.05). Serum CK-MB and cTnI concentrations and AI were significantly lower, and myocardial infarct size was smaller in O group than in M group (P<0.05). Conclusion Oxycodone produces better efficacy than morphine in reducing myocardial I/R injury in rats. Key words: Oxycodone; Morphine; Myocardial reperfusion injury