Abstract: Objective: To investigate the targeted and precise repair effect of traumatic brain injury (TBI) by intranasal transplantation of mesenchymal stem cells (MSCs).Methods: 75 male SD rats were randomly divided into sham group, model group, affected area MSCs transplantation group, intranasal MSCs transplantation group, and caudal vein MSCs transplantation group, with 15 rats in each group.The moderate TBI model was prepared by modified free-fall procedure, and MSCs (5×10⁵/cells each) were administered to rats via the affected area, intranasal route, and caudal vein, respectively.The neural function recovery of rats was evaluated by modified neurological severity score (mNSS) on day 1 and day 7 after transplantation, the recovery of brain tissue was observed by anatomy, the brain organ coefficients were compared among all groups, the transnasal entry of MSCs labeled with superparamagnetic iron oxide nanoparticles (SPIO) into the skull was observed with Prussian blue staining, and HE staining was used to observe the changes of brain histopathology in each group.Results: The results of mNSS showed that the mNSS of the model group was significantly higher than that of the sham group on day 1 and day 7 after operation (P< 0.01).Compared with the model group, mNSS in MSCs transplantation groups was significantly lower on day 1 and day 7 after operation (P< 0.01).Anatomical examination showed that the brain injury of rats in the MSC transplantation groups was significantly improved compared with that of rats in the model group on day 7 after transplantation.The brain organ coefficient of the model group was significantly higher compared with that of the sham group on day 1 after transplantation (P< 0.05).The brain coefficients of rats in the affected area MSCs transplantation group and intranasal MSCs transplantation group were significantly lower compared with those of rats in the model group (P< 0.01).Prussian blue staining showed that a large number of MSCs labeled by SPIO could be seen in the brain tissue of rats in the affected area MSCs transplantation group and intranasal MSCs transplantation group.Histopathological results revealed that compared with the model group, the brain tissue injury in the affected area MSCs transplantation group and intranasal MSCs transplantation group was reduced on day 7 after transplantation.Conclusion: Intranasal transplantation of MSCs has a good repairing effect on TBI, which can provide a theoretical basis for clinical application.