OBJECTIVE To investigate the immune efficacy of nucleic acid vaccination in mice against full-length paramyosin of Chinese Schistosoma japonicum. METHODS C57BL/6 and BALB/c mice were vaccinated intramuscularly with the nucleic acid vaccine (pCMV-SjC97) encoding the full-length gene of paramyosin of Chinese S. japonicum. Each group was immunized three times at weeks 0, 3 and 6. Mice vaccinated with pCMV blank vector served as negative control. Mice were challenged three weeks after final DNA boosting by percutaneous infection with cercariae. Six weeks after infection the mice were perfused, worm burden and eggs in the livers, spleens and intestines were counted. Sera from vaccinated mice were collected from the tail vein at weeks 0, 3, 6 and 9, respectively. RESULTS C57BL/6 mice vaccinated with pCMV-SjC97 produced predominantly IgG2a and IgG2b; whereas in BALB/c mice, IgG1, IgG2a and IgG2b antibodies. Immunization with the pCMV-SjC97 in C57BL/6 mice could confer significant worm reduction rate (35.5%-41.4%, P < 0.05) and egg reduction rate (liver: 44.5%-59.6%, P < 0.05; spleen: 56.7%-82.4%, P < 0.05; intestines: 57.9%, P < 0.05), but not in BALB/c mice. CONCLUSIONS The nucleic acid vaccine, pCMV-SjC97, could induce protective immunity in C57BL/6 mice significantly.