The microvascular function of NO during ischemia reperfusion (I/R) in intermittent hypoxia (IH) pretreated hamsters was analyzed using the non selective NO inhibitor N-nitro-L-arginine methyl ester, L-NAME, 20 mg/kg and the preferential inducible NO inhibitor S-methylisothiourea sulphate, SMT, 5 mg/kg injected before I/R. Studies were made in the hamster cheek pouch microcirculation (intravital fluorescence microscopy). IH consisted of 6 min of 8% O₂ breathing followed by 6 min of 21 % O₂ for 8 h day for 21 days. Controls (NC) were exposed to room air for the same period. Effects were characterized in terms of systemic hemodynamics, diameter, flow, wall shear stress in arterioles, capillary perfusion and the concentrations of thiobarbituric acid-reactive substances (TBARS) and plasma NO, assessed as nitrite/nitrate (NOx) levels. IH did not change arterial blood pressure and increased hematocrit and shear stress. IH increased NOx and TBARS levels and reduced arterial diameter, blood flow and capillary perfusion versus NC. Conversely, TBARS and NOx were lower during I/R in IH pretreated hamsters resulting in vasodilation and the increase of capillary perfusion and shear stress. Following IH, capillary perfusion was reduced by 24 (2.3) % and enhanced by 115 (1.7)% after I/R (P < 0.05) Both modalities of NO blockade decreased NOx generation and increased TBARS versus IH. L-NAME and SMT induced a significant decrease in arteriolar diameter, blood flow and capillary perfusion (P < 0.05). L-NAME enhanced TBARS more than SMT, and aggravated I/R damage. In conclusion, we demonstrated that preconditioning with IH greatly reduces oxidative stress and stimulates NO-induced vasodilation during I/R injury thus maintaining capillary perfusion.