Curcumin, a member of the curcuminoid family of compounds, is a yellow colored phenolic pigment obtained from the powdered rhizome of C. longa Linn. Recent studies have demonstrated that curcumin has protective effects against cerebral ischemia/reperfusion injury. However, little is known about its mechanism. In the present study, we tested the effects of curcumin in focal cerebral ischemia in rats and the possible mechanisms. Adult male Sprague-Dawley rats were treated with curcumin (100, 300 and 500 mg/kg) administered intraperitoneally after 60 min of occlusion (beginning of reperfusion). Neurological score and infarct volume were assessed at 24 and 72 h. Oxidative stress was evaluated by malondialdehyde assay and the apoptotic mechanisms were studied by Western blotting. Curcumin treatment significantly reduced infarct volume and improved neurological scores at different time points compared with the vehicle-treated group. Curcumin treatment decreased malondialdehyde levels, cytochrome c, and cleaved caspase 3 expression and increased mitochondrial Bcl-2 expression. Inhibition of oxidative stress with curcumin treatment improves outcomes after focal cerebral ischemia. This neuroprotective effect is likely exerted by antiapoptotic mechanisms.