Objective Previous studies have suggested the amelioration of lung reperfusion injury when initial reperfusion is undertaken with leukocyte-depleted blood. Pharmacologic agents, such as pentoxifylline, are also effective, but no previous studies have demonstrated which is superior. We investigated these agents in a porcine model of left single-lung transplantation. Methods Donor lungs were preserved with modified Euro-Collins solution for a mean ischemic time of 18.6 hours. Gas exchange, pulmonary vascular resistance, neutrophil elastase level, and free radical release (measured on the basis of malonaldehyde levels) were assessed over a 12-hour period. Group A (n = 5) was a control group with no interventions added. Group B was reperfused through an extracorporeal circuit incorporating a leukocyte-depleting filter for 30 minutes before conventional blood flow was restored. Group C was reperfused with the addition of intravenous pentoxifylline (2 mg · kg−1 · h−1). Results Groups B and C were similar in terms of oxygenation, pulmonary vascular resistance, and free radical release. Group B displayed increased levels of neutrophil elastase. Both groups were superior with regard to these outcome measures compared with control group A. Conclusions Pentoxifylline, when administered to recipient animals, attenuates reperfusion injury to a degree similar to that seen with leukocyte-depleted reperfusion. This technique is simple, safe, and as effective as using a more complex extracorporeal circuit incorporating a leukocyte-depleting filter to ameliorate acute lung injury.