Abstract: Objective To observe the ultrastructural changes in the muscular tissues of Duchenne muscular dystrophy mouse models with dystrophin/utrophin double-knockout (DKO) after transplantation of bone marrow-derived mesenchymal stem cells (MSCs). Methods The fifth passage of in vitro cultured MSCs from SD rats were transplanted into the DKO mice via the tail vein, and the ultrastructural changes in the gastrocnemius of the recipient rats were observed using transmission electron microscope 15 weeks after the transplantation. Results The fifth passage of the in vitro cultured MSCs growing in colonies possessed good homogeneity with low immunogenic activity for transplantation via the tail vein. After transplantation, the DKO mice exhibited improved motor function and prolonged survival period. Ultrastructural observation of the gastrocnemius of the recipient DKO mice revealed much alleviated sarcolemmal disruption, dissociation and edema of the subsarcolemmal tissues, central nuclear shift, loosening of the local myofibrils, inflammatory cell infiltration and connective tissue hyperplasia in comparison with the tissues from the DKO mice without MSC transplantation. Fusion of several immature nuclei was observed in the subsarcolemmal region. Conclusions MSCs possess strong plasticity in vitro and in vivo, and after transplantation, the MSCs may migrate to lesioned muscular tissues via the blood circulation to participate in the repair and regeneration the atrophied muscular tissues.