This study was designed to evaluate the effect of tissue-plasminogen activator (t-PA) on skeletal muscle flap perfusion after a non-occlusive thrombogenic insult to the main feeding artery. We performed a semicircular inverted suture as a thrombogenic insult to the common iliac artery. For thrombolysis tissue-plasminogen activator was infused intraarterially. After 24 hours we dissected the cremaster muscle flap and measured muscle hemodynamics and leukocyte-endothelial interactions using intravital microscopy. Capillary perfusion significantly decreased after the inverted suture over 24 hours. t-PA significantly increased capillary perfusion after the thrombogenic insult. By restoring capillary perfusion after a thrombogenic insult t-PA may increase flap survival rates.