OBJECTIVE Carthamus tinctorius L. (CT) or safflower is widely used in traditional Chinese medicine. This study investigated the effects of CT extract (CTE) on ischemia-reperfusion (I/R) brain injury and elucidated the underlying mechanism. METHODS The I/R model was conducted by occlusion of both common carotid arteries and right middle cerebral artery for 90 min followed by 24 hr reperfusion in Sprague-Dawley rats. CTE (0.2-0.6 g/kg) was administered intraperitoneally before and during ischemia, and during reperfusion period. The cerebral infarction area, neurological deficit scores, free radicals (lucigenin chemiluminescence counts) and pro-inflammatory cytokines expression were measured. RESULTS Pretreatment and treatment with CTE significantly reduced the cerebral infarction area and neurological deficits. CTE (0.4 g/kg) also reduced blood levels of free radicals and expression of tumor necrosis factor-α and interleukin-1β in the cerebral infarction area. CONCLUSIONS The reduction in I/R cerebral infarction caused by CTE is possibly associated with its antioxidation and anti-inflammatory properties.