4-hydroxybenzyl alcohol (4-HBA), one of the major active phenolic constituents of Gastrodia elata Blume, a very important traditional Chinese medicinal herb, has been shown to be an effective agent against the central and peripheral nervous disorders. In this study, we attempted to explore the possible mechanisms underlying the neuroprotection against transient focal cerebral ischemia by 4-HBA.4-HBA (25, 50 mg/kg) was given 30 min before focal ischemia in rats caused by middle cerebral artery occlusion (1 h of occlusion, 24 h of reperfusion). Under the treatment of 50 mg/kg 4-HBA, total (100.76+/-2.90 mm(3)), cortical (64.91+/-1.46 mm(3)), and sub-cortical (38.77+/-2.78 mm(3)) infarct volumes were significantly decreased in comparison to ischemia-reperfusion values. Neurological evaluation and Nissl-staining of the 4-HBA group were improved significantly compared to the untreated ischemia group. TUNEL-positive cells were reduced significantly in 4-HBA treated group. Results of immunofluorescence staining analysis and Western immunoblot indicated that 4-HBA increased the expression of Bcl-2 and inhibited the activation of caspase-3 ultimately inhibiting apoptosis. These results suggested that 4-HBA ameliorated ischemic injury induced by transient focal cerebral ischemia in rats, and this neuroprotective effect may be partly related to attenuate apoptosis pathway.