Abstract: AIM: To investigate the protective effects of different doses of hyperoxia pretreatment on the coronary artery against ischemia/reperfusion (I/R) injury in diabetic rabbits. METHODS: Adult male diabetic rabbits weighing 2-3 kg were used in this study. Diabetes mellitus (DM) was induced with IV alloxan (120 mg/kg). Eight weeks later, the animals were randomly divided into four groups (n=8 each): group S (sham operation), group OX (myocardial I/R), group HO1 and group HO2, which received hyperoxia solution (10 or 20 ml/kg), respectively, at 30 min before myocardial ischemia. A catheter was inserted into the left ventricle via the left common carotid artery for determination of left ventricular end-diastolic pressure (LVEDP), and right femoral artery was cannulated for BP monitoring. Myocardial I/R was produced by temporary ligation of the anterior descending branch of the left coronary artery (LAD) for 60 min followed by 120-min reperfusion. Myocardial ischemia was confirmed by S-T segment elevation and changes in color of myocardium. Blood samples were obtained immediately before ligation of LAD (T1), immediately before LAD ligation was untied (T2) and 120 min after LAD was untied (T3) for determination of serum NO, ET-1 and TXB2 concentrations and concentrations and coronary perfusion pressure (CPP) (CPP=LVEDP-DBP). Animals were then sacrificed and LAD was isolated. Vasomotor reaction to norepinephrine (NE) and sodium nitroprusside (SNP) was examined. RESULTS: The recovery rate of CPP was significantly better at T2 and T3 in HO2 group than in OX and HO1 groups. Serum NO concentration significantly decreased, whereas serum ET-1 and TXB2 concentration significantly increased at T2 and T3 compared to baseline values at T1 in group I/R (OX group). Serum NO concentration was significantly higher, whereas serum ET-1 and TXB2 concentration were significantly lower at T2 and T3 in HO2 group than those in OX group. Vascular tension was significantly higher in the presence of NE and lower in the presence of SNP in HO2 group compared with those in OX and HO1 groups. CONCLUSION: Pretreatment with hyperoxia solution protects the coronary artery from I/R injury in diabetic rabbits. Hyperoxia solution of 20 ml/kg has demonstrated a better protective effect than hyperoxia solution of 10 ml/kg.