The pathogenesis of generalized microvascular injury following hemorrhagic shock and total ischemia appears to be dependent on leukocytes interacting with the venular endothelium. The purpose of this study was to compare leukocyte adherence and sequestration following hemorrhagic shock with that of total ischemia in the small bowel mesentery of rats. Leukocyte adherence and sequestration was measured by direct visualization in vivo using intravital microscopy. In addition, sequestration was also quantitated by measuring tissue levels of myeloperoxidase, a marker of leukocyte infiltration. Mean arterial blood pressure was decreased to 40 mmHg for 30 min (hemorrhagic shock group). In the total ischemia group, both the superior and inferior mesenteric arteries were clamped for 30 min followed by reperfusion. Hemorrhagic shock (9.4 ± 1.5 cell/100 μm) and total ischemia (8.3 ± 3 cell/100 μm) caused a statistically significant increases in leukocyte adherence 60 min postinsult as compared with controls (.9 ± 1.5 cell/100 μm). However, the increase in leukocyte adherence appeared earlier and to a greater degree initially following total ischemia. Leukocyte sequestration as measured by intravital microscopy was significant only after total ischemia [(24.6 ± 1.7 cell/(100 μm)2; p <.01] and not hemorrhagic shock [3.4 ± .6 cell/(100 μm)2] versus controls [2.2 ± .2 cell/(100 μm)2]. This difference in sequestration was also confirmed by tissue levels of myeloperoxidase. The results of this study suggest that the microvascular response following hemorrhagic shock is different than that of total ischemia, and caution is warranted when extrapolating the experimental results of one to the other.