We have earlier reported identification, expression and purification of a 2.0kb cDNA clone coding for Brugia malayi heavy chain myosin which exhibited strong immuno-reactivity with bancroftian sera from endemic normal (EN) human subjects which are considered to be putatively immune. In the present study, immunoprophylactic characterization of B. malayi recombinant myosin was carried out in rodent models and the protective efficacy was evaluated by assessing the microfilarial burden and adult worm counts in vaccinated host after an infective larval challenge. Data indicates that immunization resulted in to a significant reduction in microfilarial burden (approximately 76%) and adult worm establishment (54-58%), accompanied with embryostatic effect (70-75%) in both the animal models. The findings suggest that immune-protection by recombinant myosin was conferred through both humoral and cellular arms of immunity as indicated by an increased antibody titer with predominance of IgG2a and IgG2b isotypes along with elevated level of IgG1 apart from significant proliferation of lymphocytes, increased nitric oxide production and profound adherence of splenocytes causing cytotoxicity to microfilariae and infective larvae. The present study indicates that the recombinant B. malayi myosin is a promising vaccine candidate against human lymphatic filarial infection.