The mesenteric microcirculation was observed via intravital microscopy to determine the effects of a period of acute exposure to hypoxia on the interactions of leukocytes within the post-capillary venule. Sprague-Dawley rats were prepared for intravital microscopy, and after a 30-minute period of observation in 21% oxygen, rats (n=6) were exposed to 12% oxygen via hood for 30 minutes and then returned to 21% oxygen for another 60 minutes. Serial video cassette recordings were taken throughout the experimental period, with the number of rolling and adherent leukocytes determined via play back offline. Data was analyzed with repeated measures ANOVA. We observed a significant increase in leukocyte rolling (before: 37.5± 21.7 cells/minute, during hypoxia: 106±56 cells/minute, after hypoxia: 120± 39 cells/minute; mean ± SD; p<0.001) and adherence (before: 1.1±1.1 cells /100μm, during: 5.8±2.4 cells /100μm, after: 3.5±1.3cells /100μm; p<0.001) to the post-capillary venule. Although hypoxic exposure did not effect systemic mean arterial blood pressure throughout the experimental period (p=0.3), a reduction in shear stress occurred during the hypoxic exposure that returned to baseline with re-exposure to room air (before hypoxia: 892±181 sec -1, during hypoxia 614±204 sec -1, after hypoxia 659±269 sec-1; p=0.014). Despite the lack of systemic hemodynamic changes, exposure to hypoxia was accompanied by increased leukocyte-endothelial cell adhesion. Adhesion occurred in the microcirculation during the period of hypoxia and persisted for the remainder of the experimental period in room air conditions. Systemic hypoxia may prime the microcirculation and increase the likelihood of gastrointestinal injury with other insults. The mechanisms by which acute hypoxia alter the interaction between the leukocyte and the endothelial cells remain to be determined.