Traumatic brain injury (TBI) sustained in a traffic accident or a fall is a major cause of death that affects a broad range of ages. The aim of this study was to investigate the therapeutic effects of intra-arterial transplantation of mesenchymal stem cells (MSCs) combined with hypertonic glycerol (25%) or mannitol (25%) in a TBI model of rats. TBI models were produced with a fluid percussion device. At 24 h after TBI, MSCs (1 x 10(6) cells/100 mu l) with glycerol or mannitol were administered via the right internal carotid artery. Rats were evaluated behaviorally and immunohistochemically, and hyperpermeability of the blood-brain barrier (BBB) induced by hypertonic solutions was explored. Compared to PBS or glycerol, the administration of mannitol resulted in increased BBB disruption. The mannitol-treated rats showed significant improvement in motor function. Intra-arterial transplantation of MSCs caused no thromboembolic ischemia. Immunohistochemically, more MSCs were observed in the injured brain tissues of mannitol-treated rats than in glycerol or PBS-treated rats at 24 h after transplantation. Intra-arterial transplantation of MSCs combined with mannitol is an effective treatment in a TBI model of rats. This technique might be used for patients with diseases of the central nervous system including TBI. (C) 2013 Elsevier Ireland Ltd. All rights reserved.