Background This study aimed at assessing the effect of noninvasive limb preconditioning on myocardial infarct size, and deter mining whether nitric oxide and neurogenic pathway play an important role in the mechanism of acute remote ischemic preconditioning (IPC). Methods Forty Wistar rats were randomly divided into fo ur experimental groups. In Group Ⅰ, the rats underwent 30-minute occlusion of the left anterior descending coronary artery, and 120-minute reperfusion. In Group PL, the rats underwent four cycles of 5-minute occlusion and reperfusion of both h ind limbs using a tourniquet before the experiment was continued as in Group Ⅰ. In Group P L-N and Group P L-H, we administered L-nitro-arginine meth yl ester (L-NAME) 10 mg/kg or hexamethonium chloride 20 mg/kg intravenously, 10 minutes before IPC. Infarct size as a percentage of the area at risk was deter mine d by triphenyltetrazolium chloride staining. Results There were no statistically significant differences in mean arterial pressure and heart rate amo ng these groups at any time point during the experiment (P>0.05). The myo cardial infarct size (IS) was decreased significantly in Group PL and Group P  L-H compared with Group Ⅰ, and the IS/AAR was 34.5%±7.6%, 35.9%±8. 6 % and 58.5%±8.5%, respectively (P<0.05). The IS/AAR was 49.1%±6.5% in Group P L-N, and there was no significant difference compared with Grou p Ⅰ (P>0.05). Conclusions Noninvasive limb IPC is effective in protecting the myocardium from ischemia reperfusion injury. Nitric oxide plays an important r ole in the mechanism of acute remote IPC, in which the neurogenic pathway is not involved . Background This study aimed at assessing the effect of noninvasive limb preconditioning on myocardial infarct size, and deter mining whether nitric oxide and neurogenic pathway play an important role in the mechanism of acute remote ischemic preconditioning (IPC). Methods Forty Wistar rats were randomly divided into In Group I, the rats underwent 30-minute occlusion of the left anterior descending coronary artery, and 120-minute reperfusion. In Group PL, the rats underwent four cycles of 5-minute occlusion and reperfusion of both h ind limbs using a tourniquet before the experiment was continued as in Group I. In Group P LN and Group P LH, we administered L-nitro-arginine meth yl ester (L-NAME) 10 mg / kg or hexamethonium chloride 20 mg / kg intravenously, 10 minutes before IPC. Infarct size as a percentage of the area at risk was deter mine d by triphenyltetrazolium chloride staining. Results There were no significant significant inferences mean arterial pressure and heart rate amo ng these groups at any time point during the experiment (P> 0.05). The myo cardial infarct size (IS) was decreased significantly in Group PL and Group P  LH compared with Group Ⅰ, and The IS / AAR was 34.5% ± 7.6%, 35.9% ± 8.6% and 58.5% ± 8.5% respectively (P <0.05). The IS / AAR was 49.1% ± 6.5% was no significant difference compared with Grou p I (P> 0.05). Conclusions Noninvasive limb IPC is effective in protecting the myocardium from ischemia reperfusion injury. Nitric oxide plays an important r ole in the mechanism of acute remote IPC, in which the neurogenic pathway is not involved.