The effects of the anti-inflammatory cytokine, IL-10, on brain injury following permanent focal ischemia were determined. Rats subjected to occlusion of the right middle cerebral artery (MCAO) were administered IL-10 (1 microg) centrally into the lateral ventricle 30 min and 3 h post MCAO or systemically into the tail vein (5 or 15 microg/h) starting 30 min post MCAO for 3 h. Brains were removed 24 h later and infarct size was measured. IL-10 administered centrally significantly (P < 0.01) reduced infarct size by 20.7% +/- 6.0 compared to vehicle. Systemic IL-10 administration at 5 and 15 microg/h significantly (P < 0.05) decreased infarct size (40.3% +/- 14.0 and 30.7% +/- 13.7, respectively). These studies indicate that an anti-inflammatory therapeutic approach using IL-10 can provide neuroprotection in ischemic stroke.