An attempt was made to evaluate the immunoprophylactic efficacy of Brugia malayi transglutaminase (BmTGA) as a DNA vaccine, for human lymphatic filariasis. BmTGA was cloned and characterized in the DNA vaccine vector pVAX1. Further, the tissue distribution study of the DNA construct, pVAX-TGA was carried out in mice and the DNA vaccine was shown to be efficiently distributed to all the organs, was accessible to the immune system, and at the same time was metabolized quickly and did not pose problems of toxicity. Intramuscular immunization in mice showed significant antibody production and splenocyte proliferation upon antigenic stimulation. The immune responses were biased towards the Th1 arm, as evaluated in terms of isotype antibody distribution and cytokine profile. Thus, analysis of the humoral and cellular immune responses indicated that BmTGA is a potent immunogen. However, protection studies as determined by the micropore chamber method using live microfilarial larvae, showed that the DNA vaccine could confer only partial protection in the mouse model. We conclude that despite the induction of sufficient humoral and cellular immune responses, BmTGA as a DNA vaccine could not confer much protection against subsequent challenge and other aspects of the immune responses need to be further investigated.