Splanchnic ischemia and reperfusion (I/R) causes tissue hypoxia that triggers local and systemic microcirculatory inflammatory responses. We evaluated the effects of hyperoxia in I/R induced by occlusion of the superior mesenteric artery (SMA) for 40 min. followed by reperfusion (120 min) in rats. Four groups were studied: a) control - undergoing anesthesia only. b) Sham - undergoing all surgical procedures without vascular occlusion and ventilated with air. c) SMA I/R and air; c) SMA I/R and ventilation with 100% oxygen started 10 min. before reperfusion. Intravital video-microscopy was employed to monitor leukocyte rolling and adhesion in mesenteric microvessels as well as pulmonary microvascular blood flow velocity (BFV) and macromolecular (FITC-albumin) flux into the lungs. We also determined pulmonary leukocyte infiltration. SMA I/R caused marked decreases in MABP and in blood flow to the splanchnic and hindquarters vascular beds and in pulmonary BFV and shear rates. This was followed by extensive increase in rolling and adhesion of leukocytes and plugging of more than 50% of the mesenteric microvasculature. SMA I/R also caused a marked increase in pulmonary sequestration of leukocytes and macromolecular leak with a concomitant decrease in circulating leukocytes. Inhalation of 100% oxygen maintained MABP at significantly higher values (P<0.001) but did not change regional blood flows. Oxygen therapy attenuated the increase in mesenteric leukocyte rolling (P<0.0001) and adherence (P<0.0001) and maintained microvascular patency at values not significantly different from shams. Hyperoxia also attenuated the decrease in pulmonary capillary BFV and shear rates, reduced leukocyte infiltration in the lungs (P<0.001) and prevented the increase in pulmonary macromolecular leak (p<0.001) mantaining it at values not different from shams. The data suggests that beneficial effects of normobaric hyperoxia in splanchnic ischemia/reperfusion are mediated by attenuation of both the local and remote inflammatory microvascular responses.