Background Tumor necrosis factor-a (TNF-a) or its mRNA expression are increased in acute nephrosis of various types including ischemia/reperfusion injury. This study was undertaken to determine whether pentoxifylline (PTX), an inhibitor of TNF-a production, provides a protective effect against hypoxia-induced cell injury in rabbit renal cortical slices. To induce hypoxia-induced cell injury, renal cortical slices were exposed to a 100% N2 atmosphere. Control slices were exposed to a 100% O2 atmosphere. Methods New Zealand white male rabbits weighing 1.5 to 2 kg were killed and the kidneys were removed rapidly. The kidneys were perfused immediately through the renal artery with an ice-cold isotonic saline solution containing 140 mM NaCl, 10 mM KCl and 1.5 mM CaCl2 to remove as much blood as possible. Induction of hypoxia-induced cell injury, measurement of cell injury in renal cortical slices, lipid peroxidation measurement, uptake of p-aminohippurate (PAH) by renal cortical slices, uptatistical analysis. Results The cell injury was estimated by measuring lactate dehydrogenase (LDH) release and p-aminohippurate (PAH) uptake. Exposure of slices to hypoxia increased the LDH release in a time-dependent manner. However, when slices were exposed to hypoxia in the presence of PTX, the LDH release was decreased. The protective effect of PTX was dose-dependent over the concentrations of 0.05-1 mM. Hypoxia did not increase lipid peroxidation, whereas an organic hydroperoxide t-butylhydroperoxide (tBHP) resulted in a significant increase in lipid peroxidation. PTX did not affect tBHP-induced lipid peroxidation. Hypoxia decreased PAH uptake, which was significantly attenuated by PTX and glycine. tBHP-induced inhibition of PAH uptake was not altered by PTX, although it was prevented by antioxidant deferoxamine. The PAH uptake by slices in rabbits with ischemic acute renal failure was prevented by PTX pretreatment. Conclusion In conclusion, PTX prevented the LDH release and reduced PAH uptake induced by hypoxia. Inhibition of slices PAH uptake caused by ischemia in vivo was attenuated by PTX pretreatment. The beneficial effect of PTX was not attributed to its antioxidant action and thus may be due to a suppression of the TNF-a production.