Inhibition of pulmonary neutrophil sequestration attenuates ischemia-reperfusion (IR) lung injury. Pentoxifylline (PTX) reduced pulmonary sequestration of neutrophils and neutrophil-dependent lung injury in several experimental settings but has never been tested in IR models. We hypothesized that PTX may have a beneficial effect on IR lung injury as measured by the coefficient of filtration (Kfc) and may reduce IR-associated sequestration of neutrophils as assessed by lung myeloperoxidase (MPO) activity and by blood neutrophil count decrease during reperfusion. Three groups of isolated blood perfused rat lungs were studied: a time control group (n = 6) was perfused for 3 h, and two groups (n = 10) subjected to 1 h ischemia were treated with PTX or saline before a 2 h reperfusion. The increase in Kfc induced by IR was reduced fivefold by PTX compared with saline (+27 +/- 8% versus +112 +/- 12%, respectively; p < 0.001), and was similar to time controls (+9 +/- 9%). After IR, MPO and blood neutrophil count decrease were lower with PTX than with saline. Changes in Kfc were correlated to the percentage decrease in blood neutrophils during reperfusion. We conclude that PTX reduced rat lung IR microvascular injury. This effect may be mainly caused by decrease in lung sequestration of neutrophils during reperfusion.