Spinal cord regeneration following treatment with a novel membrane-spanning peptide (MSP) expressing the isoleucine-lysine-valine-alanine-valine (IKVAV) epitope was assessed in Balb-c mice. After hemilaminectomy and compression injury, mice were treated with IKVAV, IKVAV-MSP, peptide or vehicle control. Functional improvement was assessed using modified Basso, Beattie, and Bresnahan Scale (mBBB) and spinal cord segments were studied histologically 28 days after injury. IKVAV-MSP group scores increased significantly compared with control groups after 4 weeks of observation (p < 0.05). The number of protoplasmic astrocytes, neurons and muscle bundle size in the IKVAV-MSP mice were significantly increased (p < 0.001; p < 0.05 and p < 0.007; respectively). This study demonstrates that it is possible to promote functional recovery after SCI using bioactive IKVAV presenting cell membrane-spanning peptides.