In free tissue transfer and replantation surgery there is a debate if any pharmacological agents should be used to improve vessel patency and tissue survival. This study was designed to investigate the direct effects of tissue-plasminogen activator (t-PA) on skeletal muscle hemodynamics and leukocyte-endothelial interactions at the microcirculatory level. We used the cremaster muscle flap model for intravital microscopy. 90 minutes after intraarterial t-PA infusion we found a significant reduction in adhering and transmigrating leukocytes counted in and in the proximity of postcapillary venules (p <0.05). These novel findings on leukocyte-endothelial interactions suggest an antiinflammatory effect of t-PA. In pathological conditions with increased leukocyte activation, such as ischemia reperfusion injury, t-PA may be beneficial for tissue survival by reducing leukocyte-endothelial interactions.