Chemotherapy of African trypanosomiasis still remains far from being satisfactory. There is the urgent need for therapeutic agents that are effective, affordable and accessible to the rural poor in Africa who bear most of the disease burden. Root preparations of Annona senegalensis Pers. is claimed by traditional medicine practitioners to be effective in the treatment of sleeping sickness. Validation of this claim, evaluation of the therapeutic effects of other parts of the plant, and standardization of the preparations are necessary in order to fully exploit the chemotherapeutic potentials of this plant. We have evaluated the chemotherapeutic effects of extracts of the leaves, whole root, root and stem bark of the plant in experimental trypanosomiasis. Crude and partially purified aqueous extracts of the leaves, at a dose of 200mg/kg body weight per day completely cured experimental Trypanosoma brucei brucei infection in mice. Sub-inoculation of blood and cerebrospinal fluid drawn from the cured mice into healthy mice failed to produce any infection within 60 days of post-inoculation. Pre-treatment of healthy mice with the crude extract before infection did not prevent establishment of infection. Administration of 5000mg/kg body weight of the crude extract did not lead to fatality in mice. Preliminary phytochemical screening showed the presence of tannin, phlobatanin, and saponin.