Background: In trichinosis, the presence of muscle larvae inside skeletal striated muscle causes loss of identity and function of myotube through the releasing of myogenin and myosin. Considering the dominant role of vaccination, research on gamma radiation-attenuated vaccine has very promising value. The goal of this study was to determine the efficacy of vaccination with radiation-attenuated Trichinella spiralis larvae on the subsequent infectivity. This goal was to be achieved by expression of myogenin, BcL-2 and DNA damages of myocytes in experimental animals. Materials and methods: Mice were randomly assigned to serve as normal control, infected control, vaccinated unchallenged and vaccinated challenged groups. Histopathological and immunohistochemical assessments of skeletal muscle tissues of diaphragm were conducted using different stains. Also, DNA damages of myocytes by comet assay were evaluated. Results: An improvement of histopathological changes and DNA damages of myocytes with significant decreased expression of myogenin and BcL-2 in vaccinated challenged group was detected. Conclusion: Vaccination with gamma radiation- attenuated larvae exerted protective effect against challenged infection. This may pave the way to new protective modality in trichinosis control.