Abstract: In vitro and in vivo trypanocidal activity of the leaf extract of Guira senegalensis against Trypanosoma brucei brucei have been investigated. Extract obtained from fresh leaves heated with methanol had highest in vitro activity against the parasite at concentration of 8.3 mg mL-1 of blood. Dried leaf methanolic extract also had in vitro activity at the same concentration after 30 min of incubation. Treatment with 100 mg/kg/day of the fresh leaf extract for five days tends to ameliorate the disease condition but did not clear the parasitaemia and pack cell volume values were not significantly affected. All other animals treated with the extract higher than the 100 mg/kg/day died before the infected controls. Addition of glycerol as an adjuvant did not show effect. The plant may be a promising trypanocide.