Spinal cord injury (SCI) is a devastating disease which poses health problems in human and veterinary medicine. SCI causes neurological disability, with loss of motor, sensory and autonomic function. This study investigated the efficacy of local treatment with IKVAV-peptide on spinal cord regeneration following compression injury at T12 vertebra in Balb-c mice. IKVAV-peptide is a membrane spanning peptide known to have a long half-life and the peptide motif IKVAV. Thirty Blab-c female mice were used. Hemilaminectomy was performed at T12 and spinal cords were compressed using extradural application of a 24 g modified aneurysm clip for 1 min in the treatment groups. After 24 hours mice were treated with one of 4 different treatments including isoleucine-lysine-valine-alanine-valaine(IKVAV), IKVAVpeptide, peptide and mannitol (vehicle). Functional improvement was assessed every day using Basso, Beattie, Bresnahan (BBB) Locomotor Rating Scale. 28 days later, the mice were euthanized, and spinal cord segments were studied histologically. Statistical analysis, one-way and two-way analysis of variance (ANOVA) and linear regression model were used to measure some parameters and describe the outcome after SCI. Over a 4weeks period, IKVAV-peptide group demonstrated statistical and histological evidence of cellular reconstruction and behavioral improvement. The BBB score in the IKVAV-peptide group increased by 5.4 (25%) points, the IKVAV and peptide groups by approximately 1 point (5%) and the mannitol group by 4 points (19%). The number of protoplasmic astrocytes in the IKVAV-peptide group was significantly increased compared to IKVAV, mannitol and normal groups but not with the peptide group (p<0.001). Neuron and muscle bundle size were also increased significantly (p<0.05 and p<0.007, resp.) in the IKVAV-peptide group compared to other treatment groups. The treated control groups showed cellular and gross damages including neuron inactivation and muscle atrophy, gliosis and inability of movement. / Graduation date: 2013