Acetylsalicylic acid (ASA) is neuroprotective through various pharmacological action sites. We used a temporary middle cerebral artery occlusion (tMCAO) model in 56 Wistar rats to assess whether repeated ASA injections at 30 min, 6 h, 1, 2, 3, and 4 days after stroke onset are neuroprotective. Animals were sacrificed 5 days after MCAO; infarct size was analyzed with 2,3,5-triphenyltetrazolium chloride staining. As compared to saline (164+/-13 mm(3), n=14), only repeated injections of 40 mg/kg ASA (79+/-18 mm(3), n=14, P=0.0029), but not of 20 mg/kg ASA (129+/-19 mm(3), n=15), reduced infarct volume significantly. No significant change was noted with 40 mg/kg ASA injected only once at 30 min after MCAO (117+/-16 mm(3), n=13).