The aims of the study were to assess the effect of praziquantel on Schistosoma japonicum infection in pigs, and to elucidate the level of resistance to reinfection after treatment. Pigs were given a single infection with S. japonicum followed by a praziquantel treatment (40 mg/kg) week 8, reinfection week 12 and perfusion week 20 post-primary infection. Relevant control groups were included. Worm burdens, faecal and tissue egg counts, gross- and histopathology of the liver and specific liver enzymes were assessed. The results showed a 100% cure rate of praziquantel against S. japonicum in pigs. Worm nodules were present in equal numbers in the intestinal wall 4 and 14 weeks post-treatment. Treatment did not significantly reduce the number of tissue eggs neither 4 nor 14 weeks post-treatment. No worm nodules or worm-induced lesions were found in the livers of the treated pigs and the levels of liver enzymes were comparable in treated and non-treated infected pigs. Periportal and septal fibrosis regressed following treatment. Faecal egg counts were significantly reduced 2 (56%) and 4 (82%) weeks after treatment. Challenge infection 4 weeks post-treatment did not result in establishment of new worm pairs. Praziquantel proved to be highly effective against S. japonicum in pigs without causing pathological side-effects in the liver.