Background: Pentoxifylline (PTX) is used in human for intermittent claudication and cerebral vascular disorders including cerebrovascular dementia. It also inhibits the synthesis of tumor necrosis factor-α (TNF-α), which is believed to be neurotoxic in animal models of cerebral ischemia. The objective of this study was to examine the role of PTX on ischemia/reperfusion injures in rat model of transient focal cerebral ischemia induced by middle cerebral artery occlusion (MCAO). Methods:Male Sprague Dawley rats (n=31) were assigned to sham, saline or PTX (30 or 60 mg/kg)-treated groups. Ischemia was induced by MCAO, followed by 24-hrs reperfusion. Intraperitoneal saline or PTX was administered at 30 min before ischemia. Neurological deficit score test (NDS) was performed after 24-hrs, and the animals was sacrificed for evaluation of cortical and striatal infarct volumes using triphenyltetrazolium chloride staining. Results: The sham group did not have neural dysfunction or cerebral infarction. Cortical infarct volumes in 30 or 60 mg/kg PTX-treated groups, 149±12 and 129±19 mm3 respectively, were significantly lower than that of saline-treated group (208 ±12 mm3). Similar results were also obtained about the striatal infarct volumes (39±5 and 40±6 vs. 58±5 mm3). However, there was no significant difference among the neurological dysfunctions from saline and PTX-treated rats. Conclusion: the results of this study indicate that pentoxifylline reduced cerebral infarctions, possibly by diminishing the TNF-α-induced neurotoxicity in transient focal cerebral ischemia. This finding also suggests that pentoxifylline might be suitable for clinical trials.