To investigate the effects of idebenone on cognitive function and expression of growth associated protein-43 (GAP-43) and synaptophysin P38 in the hippocampus of vascular dementia (VD) rats. Methods: Sixty SD rats were randomly divided into the sham operation group, model group, and idebenone group with 20 rats in each group. The VD rat model was established by modified 2-vessel occlusion (2-VO) method. Idebenone group rats were given intraperitoneal injections of idebenone at 10 mg/ kg once per day for 30 consecutive days, and model group and sham operation group rats were given equivalent doses of normal saline. The differences in learning and memory capabilities were evaluated by water maze. The expression of GAP-43 and synaptophysin P38 in the hippocampus was measured by immunohistochemistry. The ultrastructure of synapses was observed by transmission electron microscopy. Results: The model group showed increased escape latency and decreased platform crossings in the water maze compared to those in the sham operation and idebenone groups (both P<0.05). The escape latency and platform crossings of the idebenone group and sham operation group showed no significant difference (P> 0.05). Compared with that of sham operation group and idebenone group rats, the GAP-43 and synaptophysin P38 expression in the hippocampus of model group rats was decreased (P<0.05). Hippocampus expression of GAP-43 and synaptophysin P38 in idebenone group rats was increased compared to that of sham operation group and model group rats (P<0.05). Electron microscopy showed that in model group rats, synaptic structure in the hippocampus was damaged while in idebenone group rats, synapses in the hippocampus were abundant in quantity and complete in structure. Conclusion: Idebenone may improve learning and memory capabilities in VD rats via mechanisms that involve up-regulating GAP-43 and synaptophysin P38 expression.