Aim To study the effect of aerobic exercise on memory ability of mice with vascular dementia. Methods To expose the bilateral common carotid arteries of KM mouse, repeatedly occlusion of common carotid artery and blood letting in caudal vein were made to establish a mouse model of vascular dementia. The mice were randomly divided into three groups:sham group, model group, and aerobic exercise group. Aerobic exercise began on the second day after operation for 7 weeks. Behavioral tests were performed after the training. Brain tissue samples (hippocampus, prefrontal lobe, whole brain and serum) were collected 30 days after the operation. The pathological changes of hippocampal CA1 region were observed by HE staining. The apoptosis of hippocampal CA1 region was detected by TUNEL method. Western blot and ultraviolet spectrophotometer were used to detect the expression of Bcl-2, Bax, malondialdehyde (MDA), superoxide dismutase (SOD), growth-related protein-43 (GAP-43), brain-derived neurotrophic factor (BDNF), acetylcholine synthase (ACHE), acetylcholine transferase (CHAT), synaptophysin (SYP), nerve cell adhesion molecule (NCAM) and nerve cell adhesion molecule receptor 2B (NR2B). Results Compared with the sham group, the time of fear memory in the model group was significantly shortened. The neuronal cells in the hippocampus of the model group were severely damaged and the number of apoptotic cells was increased, the expression of MDA and ACHE protein was significantly increased, the levels of synaptophysin, NCAM, NR2B, SOD, BDNF, CHAT, GAP-43 and Bcl-2 protein expression decreased, Bax protein expression did not change significantly. Compared with the model group, the time of fear memory in the aerobic exercise group was significantly prolonged, the histopathological changes in the hippocampus of the brain were improved, the number of apoptotic cells was decreased, the expression of MDA and ACHE protein was significantly decreased, and the levels of synaptophysin, NCAM, NR2B, SOD, BDNF, CHAT, GAP-43 and Bcl-2 protein expression increased, while Bax protein expression did not change significantly. Conclusion Aerobic training may improve the learning and memory function of vascular dementia mice by up-regulating the expression of Bcl-2, SOD, BDNF, CHAT, GAP-43, SYP, NCAM and NR2B, down-regulating the expression of MDA and ACHE, reducing the damage of free radicals and apoptosis of hippocampal neurons.