Objective To explore the mechanism of occurrence of neurological sequelae after SCI and the means of intervention by establishing a spinal cord injury (SCI) mouse model and using MMP-9 protein expression as an entry point to study its expression in the model and its relationship to blood-spinal cord barrier (BSCB) damage and neuronal apoptosis.Methods SCI model was constructed and the expression of vascular basement membrane marker Laminin-α2 and tight junction protein ZO-1 was observed by immunofluorescence staining, followed by the detection of the changes in MMP-9 expression after SCI at the protein and mRNA levels, and the main source cells of MMP-9 were identified by immunofluorescence. The relationship between MMP-9 and BSCB destruction was observed by transmission electron microscopy and wet and dry weight measurements using the MMP-9 inhibitor MMP-9-IN-1. The relationship between MMP-9 and tissue apoptosis after SCI was detected using Western Blot, and the correlation between MMP-9 and neurological sequelae was clarified by TUNEL/NeuN staining.Results BSCB showed significant damage 3 days post-SCI (P<0.05), featuring discontinuous basement membrane, tight junction loss, and FITC-Dextran leakage. MMP-9 increased significantly at 6h post-SCI (P<0.05), peaked at 1 day, and was primarily localized to activated microglia. MMP-9 inhibition reduced spinal edema (P<0.05), restored BSCB integrity (P<0.05), and decreased neuronal apoptosis (P<0.05). Conclusion The increased expression of microglia-derived MMP-9 after SCI disrupts the BSCB leading to spinal cord edema and causes neuronal apoptosis, and the inhibition of MMP-9 activity after SCI can effectively improve the functional impairment after SCI