OBJECTIVE: To detect the changes in learning and memory ability, the injury of hippocampal neurons and the intracephalic peroxidation level in model rats with chronic cerebral ischemia, and to investigate whether 2,3,5,4′- tetrahydroxystilbene-2-O-β-D-glucoside (TSG), the main effective component of polygonum multiflorum, has significant improving and protecting action in the above aspects. METHODS: The chronic cerebral ischemia models were induced by the 8-week permanent ligation of bilateral carotid arteries in male SD rats. Morris water maze and the step-through test were used to detect the learning and memory ability. Nissl's staining was used to show the status of hippocampal neurons. The biochemical methods were used to examine the MDA content and CSH-PX activity in cerebral cortex and hippocampus. RESULTS: In model rats, the spacial learning and memory ability, passive avoidance learning and memory ability were severely impaired, hippocampal neurons and Nissl's bodies were notably reduced, GSH-PX activity significantly decreased, and MDA level increased. The administration of TSG markedly improved the learning and memory ability of model rats, mitigated the injury of hippocampal neurons, increased the GSH-PX activity and decreased the MDA level in both cortex and hippocampus. CONCLUSION: TSG can improve the learning and memory ability of chronic cerebral ischemic model rats, mitigate the injury of hippocampal neurons, increase the antioxidation ability and decrease the peroxidation level in cerebral cortex and hippocampus.