Transplantation of mesenchymal stem cells (MSCs) derived from bone marrow has been shown to improve functional outcome in spinal cord injury (SCI). Systemic delivery of MSCs results in therapeutic benefits in a number of experimental central nervous system disorders. In the present study we intravenously administered rat MSCs derived from bone marrow at various time points after induction of a severe contusive SCI in rat to study their therapeutic effects. MSCs were systemically delivered at varied time points (6 h to 28 days after SCI). The spinal cords were examined histologically 6 weeks after SCI. Stereological quantification was performed on the spinal cords to determine donor cell (MSCs transduced with the LacZ gene) density in the lesions. Light microscopic examination revealed that cavitation in the contused spinal cords was less in the MSC-treated rats. A limited number of cells derived from MSCs (LacZ+) in the injury site expressed neural or glial markers. Functional outcome measurements using the Basso–Beattie–Bresnehan (BBB) score were performed periodically up to 6 weeks post-SCI. Locomotor recovery improvement was greater in the MSC-treated groups than in sham controls with greatest improvement in the earlier post-contusion infusion times. The availability of autologous MSCs in large number and the potential for systemically delivering cells to target lesion areas without neurosurgical intervention suggests the potential utility of intravenous cell delivery as a prospective therapeutic approach in acute and subacute SCI.