A standardized extract of Gingko biloba, EGb 761, has been shown to exert a neuroprotective effect against permanent and transient focal cerebral ischemia. This study investigated whether EGb 761 modulates Bcl-2 family proteins in ischemic brain injury. Male adult rats were treated with EGb 761 (100 mg/kg) or vehicle prior to middle cerebral artery occlusion (MCAO), brain tissues were collected 24 hours after MCAO. EGb761 administration significantly decreased the number of TUNEL-positive cells in the cerebral cortex. Ischemic brain injury induced decrease of Bcl-2 and Bcl- X L levels. EGb 761 prevented not only the injury-induced decrease of Bcl-2 and Bcl- X L levels, but also the injury-induced increase of Bax. Moreover, in the presence of EGb 761, the interaction of Bad and Bcl- X L decreased compared to that of vehicle-treated animals. In addition, EGb 761 prevented the injury-induced increase of cleaved PARP. The finding suggests that EGb 761 prevents cell death against ischemic brain injury and EGb 761 neuroprotection is affected by preventing the injury-induced increase of Bad and Bcl- X L interaction.