Abstract: Objective To explore the neuroprotective effect and possible mechanism of Liraglutide in the rat model of spinal cord injury (SCI). Methods Fifty-four SD rats were randomly divided into three groups:sham operation group (n=18), spinal cord injury (SCI) group (immediately received 50μg/kg saline injection intraperitoneally after injury, n=18) and Liraglutide group (immediately received 50μg/kg Liraglutide injection intraperitoneally after injury, n=18). Spinal cord injury model was established using Allen's method. The rats were sacrificed and the spinal cord tissue were taken out 3 days after injury. Western blot was used to analyze the LC3-Ⅱ and caspase-3 expression. Immunofluorescent double labeling was used to detect the autophagy positive neurons and neuronal apoptosis. Finally, behavioral assessment with Basso Beattle Bresnahan locomotor rating scale (BBB) was done at 1 d, 3 d and 7 d after injury. Results Compared with sham group, the expression of LC3-Ⅱ, the level of caspase-3 and the number of autophagy positive neurons and neuronal apoptosis increased significantly in SCI group (P< 0.01), while the BBB score decreased significantly (P< 0.01). Furthermore, compared with SCI group, Western blot showed that the expression of LC3-Ⅱincreased while the level of caspase-3 decreased in Liraglutide group (P< 0.01). Immunofluorescent double labeling showed that the number of autophagy positive neurons enhanced significantly (P< 0.01) and the neuronal apoptosis in Liraglutide group reduced significantly compared with SCI group (P< 0.01). Finally, behavioral assessment showed that animals in Liraglutide group achieved significant increase in BBB score on 3 d and 7 d (P< 0.01). Conclusion Liraglutide promotes neuronal autophagy, decreases neuronal apoptosis and improves the locomotor function after SCI. Liraglutide may be a new candidate for clinical application in the treatment of SCI.