Our recent study has demonstrated anti-edematous effect of Pentoxifylline (PTX) on focal ischemic brain injury, but its time-dependent therapeutic effects are not clear. Under chloral hydrate anesthesia, transient focal cerebral ischemia was induced in 47 male rats by 60 min of middle cerebral artery occlusion (MCAO), followed by 23 h of reperfusion. Saline or PTX (60 mg/kg, ip) was given at the beginning or at 1 or 3 and/or 6h after induction of ischemia. Twenty-hour post-ischemia percentage of brain water content (edema) was determined using the dry-wet method. Administration of PTX at the beginning or 1 or 3 and/or 6h of MCAO, significantly reduced cerebral edema (P<0.001). These findings showed that PTX reduced post-ischemic brain edema with a 6-h therapeutic time window in transient focal stroke.