Ischemic preconditioning (IPC) renders tissue resistant to the deleterious effects of prolonged ischemia and reperfusion by prior exposure to brief, repeated periods of vascular occlusion. Although the mechanism by which IPC exerts its effect is unclear, it likely mediates an attenuation in capillary no-reflow. Tissue oximetry provides a potential technique to assess microvascular flow during ischemia/reperfusion and to measure the effect of IPC on muscle tissue oxygenation. The authors aimed to (a) establish that tissue oximetry is a sensitive method to assess the "no-reflow" phenomenon in skeletal muscle; and (b) to test the hypothesis that IPC would increase tissue oxygenation during reperfusion. In Group 1 (n = 5), the rabbit rectus femoris muscle was subjected to 2-hr ischemia. In Group 2 (n = 5), the muscle was subjected to 3.5-hr ischemia. In Group 3 (n = 6) the muscle was subjected to 3.5-hr ischemia preceded by three cycles of 10 min of pedicle occlusion and 10 min of reperfusion. Muscle oxygen tension was continuously monitored during the ischemic interval and for 6 hr of reperfusion. It was found that muscle oxygen tension in the flap at 5, 10, 30, 60, and 360 min after reperfusion was significantly decreased after 3.5-hr ischemia, compared with 2-hr ischemia (p < 0.05). Muscle oxygen tension at 30 and 60 min after reperfusion was significantly improved in the preconditioned group (p < 0.05). The results suggest that tissue oximetry is a sensitive method to assess tissue perfusion in reperfused skeletal muscle. Ischemic preconditioning improves tissue oxygenation during reperfusion following prolonged ischemia, which likely reflects an attenuation in capillary no-reflow.