In a previous study, we reported that the administration of pyridoxine (vitamin B(6)) to mice for 3 weeks significantly increased cell proliferation and neuroblast differentiation in the dentate gyrus without any neuronal damage. In the present study, we investigated the restorative potentials of pyridoxine on ischemic damage in the hippocampal CA1 region of Mongolian gerbils. Gerbils were subjected to 5 min of transient ischemia, and surgical operation success was assessed by ophthalmoscope during occlusion of common carotid arteries and spontaneous motor activity at 1 day after ischemia/reperfusion. Pyridoxine (350 mg/kg) or its vehicle (physiological saline) was intraperineally administered to ischemic gerbils twice a day starting 4 days after ischemia/reperfusion for 30 or 60 days. The repeated administration of pyridoxine for 30 and 60 days significantly increased doublecortin-immunoreactive neuroblasts in the dentate gyrus and increased NeuN-immunoreactive mature neurons and βIII-tubulin-immunoreactive dendrites in the hippocampal CA1 region. Furthermore, brain-derived neurotrophic factor (BDNF) protein levels were significantly increased in pyridoxine-treated groups compared to those in the vehicle-treated groups. These results suggest that chronic administration of pyridoxine enhances neuroblast differentiation in the dentate gyrus and induces new mature neurons in the hippocampal CA1 region by up-regulating BDNF expression in hippocampal homogenates.