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Enteric Nervous System (ENS) is of special interest as it is the only substantial grouping of neurons outside the CNS. ENS alterations participate in the motility disorders. Colostomy is a lifesaving surgery that treats many diseases and problems. The aim of this study was designed to investigate the histological changes that could occur in the myenteric plexus in case of colostomy and to evaluate the therapeutic role of mesenchymal stem cell. Thirty five healthy adult Wistar male albino rats were classified into three groups: Group1 (control) was equally subdivided into negative control (1a), sham operated-untreated (1b) and vehicle-treated subgroups (1c). Group2 (colostomy group): subjected to colostomy operation. Group3 (BM-MSCs-treated group): subjected to colostomy operation and then treated with undifferentiated BM-MSCs. At the end of the experiment, the rats were sacrificed and specimens from different levels of GIT were prepared for histological and immunohistochemical examination. The results were histomorphometrically and statistically analyzed. Light microscope examination of Group2 showed irregular connective tissue capsule of myenteric plexus in different GIT levels. The neurons and glial cells appeared small in size, irregular in shape with separation between the cells. In Group3, the same levels preserved normal myenteric plexuses structure. Immunoperoxidase reaction for synaptophysin revealed weak positive immunoreaction in the colostomy group that returned moderate to strong positive reaction in BM-MSCs-treated group. Additionally, fluorescent microscope examination revealed PKH26 labled cells that appeared as bright red dots in the myenteric plexuses between smooth muscle fibers in BM-MSCs-treated group. In conclusion, colostomy adversely affected the histological structure of myenteric plexus in different GIT levels. Mesenchymal stem cell therapy could be promising as an adjuvant treatment for rescuing ENS in case of colostomy.