Background: Trichinella spiralis causes trichinosis through ingestion of pork contaminated by its infective larvae, resulting in intestinal and muscular phases of infection in the same host. Stem cells (SCs) treat some diseases due to their capacity for trans-differentiation and immunomodulation. Objective: To assess the therapeutic impact of mesenchymal stem cells (MSCs) during intestinal and muscular stages in T. spiralis-experimentally infected mice; used alone as monotherapy or combined with mebendazole (MBZ). Material and Methods: Forty albino mice were used to obtain bone marrow MSCs. Another 100 albino mice were divided into 2 groups 50 mice each simulating intestinal (a) and muscular (b) phases. Each group was further subdivided into 5 subgroups, 10 mice each as follows: G1a and G1b: negative non infected control; G2a and G2b: positive infected control; G3a and G3b: infected and MBZ treated; G4a and G4b: infected and MSCs tested; and G5a and G5b: infected and combined MBZ and MSCs therapy tested. Mice of intestinal phase were sacrificed on 7th day post-infection (PI) while mice of muscular phase were sacrificed on 49th day PI. Assessment was done by parasitological assessment (the number of adult worms in the intestine in groups (a) and the number of encysted larvae in the diaphragm in groups (b); histopathological and histochemical assessment of all groups using hematoxylin and eosin (H&E) and Feulgen stains of different mice tissues and ultrastructural assessment using transmission electron microscope (TEM). Results: The combined therapy was potent; it showed the highest significant reduction in the number of intestinal worms and encysted muscular larvae with preservation of the different tissues elements as investigated by different stains and TEM. Conclusion: MSCs can be used as additive/synergistic therapy in the treatment of trichinosis.