Crude ethanolic extract of Indian medicinal plant, Desmodium gangeticum (A001) and its three fractions-hexane (F002), n-butanol (F003) and aqueous (F004) were evaluated chemoprophylactically and chemotherapeutically against experimental visceral leishmaniasis in hamsters. Ethanolic extract showed 41.2+/-5.3% inhibition of parasite multiplication when administered at a dose of 250 mg/kgx2 on day -7 and +7 of Leishmania donovani challenge. Its n-butanol fraction exhibited better efficacy than the ethanolic extract to the tune of 66.7+/-6.1% inhibition when administered at similar dose schedule. But the other two fractions failed to exert any action prophylactically. F003 also imparted significant (P<0.001) non-specific resistance to peritoneal macrophages against Leishmania infection. F003 also showed moderate antileishmanial activity when tested against established infection of Leishmania donovani in hamsters but the rest three fractions failed to show any significant inhibition of parasite multiplication. These findings revealed that this plant has potential prophylactic and therapeutic efficacy against Leishmania infection and warrants detailed investigations on its possible immunopotentiatory actions.