The role of thrombolysis in reestablishing patency in the microcirculation following ischemia, and thereby improving the efficacy of agents attenuating reperfusion injury, such as the oxygen free radical scavenger, superoxide dismutase (SOD), was investigated in a rat model. Abdominal skin flaps were subjected to normothermic ischemia induced by complete occlusion of the pedicle for periods of 12, 13, 14 16, 18, 20, 22, and 24 hr. In Group 1 (n = 64) all animals received flap washout using 100,000U urokinase (manual injection) followed by 7,500 IU SOD given intra-arterially immediately prior to reperfusion. Animals in Group 2 received flap washout consisting of 100,000U urokinase given via a pressurized delivery system, followed by 7500 IU SOD. Results demonstrated a statistically significant improvement in flap survival in Group 2. The authors concluded that thrombolytic therapy may be useful in improving the delivery of agents, such as SOD, which attenuate reperfusion injury in skin flaps.