OBJECTIVE To explore the repair of spinal cord injury (SCI) in rats by umbilical cord mesenchymal stem cells (UCMSCs) through the p38mitogen-activated protein kinase (MAPK) signaling pathway. METHODS A total of 45 healthy adult male Sprague-Dawley rats weighing 180-220 g and aged 6-8 weeks old were randomly divided into group A (SCI model + transplantation of UCMSCs, n=15), group B (sham operation), and group C (SCI model + injection of an equal dose of DMEM, n=15) using a random number table. The morphology of spinal cord tissues was observed via hematoxylin-eosin (HE) staining, and the protein expression of phosphorylated p38 (p-p38) in spinal cord tissues, the expression of glial fibrillary acidic protein (GFAP) in the injury region, and the spinal cord neuronal apoptosis were detected via Western blotting, immunofluorescence labeling and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay, respectively. RESULTS In group B, there was no significant damage to the structure of spinal cord tissues. In group C, the spinal cord tissues had a disordered structure and significant fragmentation, the damage to grey matter was the greatest. Also, almost all of the grey matter was destroyed and dissolved, with a large number of scars and cavitation, and it was hard to distinguish the gray matter and white matter. In group A, the spinal cord tissues had a clear structure, there were smaller necrotic cavitation regions in the grey-white matter, and the number of cavitation significantly declined compared with that in group C. The results of immunofluorescence assay revealed that the expression of GFAP in spinal cord tissues was the lowest in group B, while it was remarkably decreased in group A compared with that in group C (p<0.05), suggesting that injecting UCMSCs via the caudal vein can prominently reduce the expression of GFAP in spinal cord tissues. Moreover, the spinal cord neuronal apoptosis rate was (4.21±0.19), (0.72±0.21) and (4.57±0.31), respectively, in group A, group B, and group C. It can be seen that the spinal cord neuronal apoptosis rate significantly declined in group A due to the treatment with UCMSCs. Also, the significant difference compared with that in group C, while it was significantly increased in group A compared with that in group B, but lower than group C (p<0.05). According to the results of Western blotting, the protein expression of p-p38 in spinal cord tissues was remarkably decreased in group B compared with that in group A and group C (p<0.05), while it was also markedly decreased in group A compared with that in group C (p<0.05), indicating that injecting UCMSCs via the caudal vein can significantly lower the protein expression of p-p38 in spinal cord tissues. CONCLUSIONS UCMSCs promote the recovery of neurological function, inhibit the p38 MAPK pathway activated after SCI, and reduce the spinal cord neuronal apoptosis in SCI rats.