P Pe en nt to ox xi if fy yl ll li in ne e d do oe es s n no ot t p pr ro ot te ec ct t a ag ga ai in ns st th hy yp pe er ro ox xi ic c l lu un ng g i in nj ju ur ry y i in n r ra at ts s The drug pentoxifylline has been shown to have a protective effect in other models of lung injury. We sought to determine whether pentoxifylline protects against hyperoxic lung injury in rats by decreasing the accumulation of neutrophils within the lung. A total of 84 rats were studied. Twenty four rats were randomized into four groups. Two groups of rats were pretreated for 48 h with either pentoxifylline (20 mg·kg -1 ) or saline, and then exposed to >95% O 2 for 60 h while treatments continued. Two groups of control rats received the same treatment regimens as the O 2 -exposed animals, but breathed room air. Neutrophil accumulation in the lung was quantified both by histology and myeloperoxidase activity.Lung neutrophil accumulation increased in the oxygen-exposed group receiving pentoxifylline as compared to oxygen-or air-exposed rats receiving saline injections. Total glutathione was higher in lung homogenates from the hyperoxic, pentoxifylline-treated group than in homogenates from the other three groups. To study survival, 60 rats were exposed to >95% O 2 for 120 h, 30 rats were pretreated with pentoxifylline, and 30 received saline. Survival after 120 h of exposure to hyperoxia was not altered by pentoxifylline treatment (pentoxifylline treated: 6 out of 30 survived; saline treated: 2 out of 30 survived).We conclude that pentoxifylline does not reduce mortality or lung injury in rats exposed to hyperoxia and is associated with an increase in lung neutrophil accumulation.