Objective: Traumatic brain injury (TBI) is a major cause of mortaliy worldwide. The clinical studies have proven cell therapy as a major option to improve the brain function post trauma, and by possible regeneration of the nervous system.The aim was to investigate the role of intravenous administration of mesenchymal stem cells (MSCs) after experimental TBI in rats. Materials and Methods: Rats were divided into two groups of TBI + PBS (control) and TBI + MSC (experimental). TBI was done based on model of Foda- Marmarou. MSCs were exposed with bromodeoxyuridine (Brdu) 48 hours before intravenous injection. The experimental group received 3×106 rat MSCs, labeled with Brdu, and PBS was injected to control group, into the lateral tail vein, 24 hours after TBI. The neurological severity score (NSS) was performed to evaluate the neurological function at 0, 1, 7 and 14 days after TBI. The rats were killed 14 days after TBI. MSCs migration and their differention to neurons and astrocyte cells were examined with immunohistochemistry technique. Results: Results from NSS showed no significant differences between the groups of control and experimental at 1 and 7 days (3.5 ± 1.41 vs. 5.63 ± 2.44, p=0.06) and (2 ± 1.69 vs. 3.62 ± 1.99, p=0.06), respectively. However, motor deficits decreased significantly in the experimental rats when compared with control group at 14 days (0.75 ± 0.7 vs. 2.75 ± 1.83, p=0.01). Immunohistochemical studies showed that Brdu positive MSCs migrated via venous system to the cerebral tissue. Also, migrated MSCs to the injured brain were able to express neuronal (NeuN) and astrocytes (GFAP) markers. Conclusion: Intravenous administration of MSCs seems to improve the functional recovery and neural cells regeneration after TBI in animal model. MSCs application may be suitable as therapeutic strategy for regeneration of CNS after TBI.