Objective To evaluate the role of nitric oxide (NO) in sevoflurane preconditioning-induced amelioration of myocardial ischemia-reperfusion injury (I/R) in rabbits. Methods Forty healthy New Zealand white rabbits weighing 2.1-2.9 kg were randomly divided into 5 groups (n=8 each): group Ⅰ I/R;group Ⅱ sevoflurane preconditioning (SEV);group Ⅲ L-NAME;group Ⅳ SEV + L-NAME and group Ⅴ L-NAME + SEV. The animals were anesthetized with pentobarbital, tracheostomized, intubated and mechanically ventilated (VT=15 ml/kg, RR = 35 bpm, FiO2 = 50% ). PET CO2 was maintained at 30-35 mm Hg. MAP, HR, LVSP and +dp/dtmax were monitored. Myocardial I/R was produced by occlusion of left anterior descending branch of coronary artery for 45 min followed by 3 h reperfusion. In group SEV(group Ⅱ) 1.7% SEV was inhaled for 30 min followed by 15 min washout before myocardial I/R. In group L-NAME (group Ⅲ) L-NAME (the NOS inhibitor) 1 mg/kg was given iv 5 rain before I/R. In group Ⅳ L-NAME 1 mg/kg was given iv between SEV preconditioning and I/R and in group Ⅴ L-NAME 1 mg/kg was given iv before SEV preconditioning and I/R. MAP, HR, LVSP and + dp/dtmax were recorded at 30 min stabilization (baseline), at the end of 45 min myocardial ischemia (T1), and at 60, 120 and 180 min of reperfusion (T2-4). Blood samples were taken at 1"4 for determination of plasma concentration of cTnT, activation of CK-MB and LDH. The hearts were then removed for determination of infarct size (IS) and the area at risk of ischemia (AAR). IS/AAR was calculated.Results + dp/dtmax was significantly higher, the plasma concentration of cTnT and activity of CK-MB and LDH and IS/AAR were significantly lower at T4 in group SEV (group Ⅱ) than in group I/R (group Ⅰ) (P<0.05). There were no significant differences in the hemodynamics, plasma cTnT concentration, CK-MB and LDH activities and IS/AAR between group Ⅰ (I/R) and group Ⅲ,Ⅳ and Ⅴ (P0.05). Conclusion NO is involved in the protective effect of SEV preconditioning against I/R injury.