Objective: To study the effects and possible mechanisms of effective composite of Naodesheng (脑得生, NDS) on permanent cerebral ischemia-induced injury in rats. Methods: Male Sprague-Dawley rats with middle cerebral artery occlusion (MCAO) were established with the modified suture method, and they were randomly divided into the following groups: the sham-operated group, the model group, the Nimodipine group (0.012 g/kg), the NDS group (1.075 g/kg), the total extracts group (0.23 g/kg), the high-dose NEC group (0.07 g/kg), the middle-dose NEC group (0.02 g/kg), and the low-dose NEC group (0.007 g/kg). The aforesaid medicines were administered at the 2nd, 4th, and 24th h after focal cerebral ischemia, and the infarction size and water content in the brain were evaluated at the 26th h after MCAO. Then, after oral administration once daily for 7 successive days, the changes in the degree of neurological deficit, oxidative stress, and apoptosis were measured on the 7th day. Results: NEC could significantly reduce the infarction size after focal cerebral ischemia, and slightly relieve water content in the brain, significantly alleviate neurological function impairment, increase the levels of superoxide dismutase (SOD) and adenosine triphosphate enzyme (ATPase) activity, and decrease the content of malondialdehyde (MDA). NEE; could also extenuate Bax and caspase-3 expression in the hippocampus tissue of the ischemic region. As compared with the three NEE; treated groups, the highdose NEC showed better efficacy. Conclusions: NEE; could significantly reduce brain injury induced by ischemia; its mechanism was closely associated with hindering oxidative stress and apoptosis. The effective compositeguided methodology is a feasible tool to improve the neuro-protective properties of the Chinese medicine prescription NDS against focal cerebral ischemia in rats.