Objective To investigate the effects of bone marrow mesenchymal stromal cells (BMSCs) transplantation after mannitol pretreatment on behavioral performance and synaptophysin expression in the CA3 region in hippocampus of vascular dementia (VD) rats.Methods The BMSCs of rats were isolated and purified by the whole bone marrow adherence method.The rats were subjected for permanent ligation of bilateral common carotid arteries at an interval of 3 days for each carotid artery.At the same time,Sham group was set in parallel.Four weeks after modeling,the VD rats were divided randomly into five groups:(1) VD control group; (2) culture media group; (3) mannitol group; (4) BMSCs group;(5) mannitol with BMSCs group.Morris water maze performance and synaptophysin expression in the CA3 region in hippocampus were observed at 4 weeks after transplantation.Results The morris water maze performance significantly improved in mannitol with BMSCs group when compared with BMSCs group,VD control group,culture media group,mannitol group.Moreover,the escape latency of fifth day decreased significantly ((9.3 ±2.9),(14.1 ±3.5),(23.5 ±4.4),(22.8 ±4.4),(23.2 ±2.8) s,F =43.900,P =0.000)),and the platform quadrant residence time increased significantly ((40.8 ± 6.3),(34.9 ±5.8),(26.4±4.8),(27.4 ±7.0),(28.5 ±6.2) s,F=13.000,P=0.000)).The synaptophysin expressions of the hippocampal CA3 region were significantly increased in the mannitol with BMSCs group (39 624 ± 7798) when compared with BMSCs group,VD control group,culture media group,mannitol group (27060 ±4668,18 294 ±6446,19 956 ±4244,18 946 ±4953,F =39.206,P =0.000).Conclusions Intravenous BMSCs transplantation after mannitol pretreatment improves the behavioral performance of VD rats and facilitates the synaptophysin expression of hippocampal CA3 region in VD rats than BMSCs transplantation alone.Mannitol pretreatment can amplify the therapeutic effect of intravenous BMSCs transplantation in VD rats.