The trypanocidal activity of different fractions of hydroethanolic root extract of Mitragyna ciliata Aubrev and Pellegr (Rubiaceae) were evaluated in rats infected with Trypanosoma brucei field isolates from a cow. Oral administration of the fractions at a dose of 100 mg/kg for 5 days (10 days post-infection) indicated that only butanol fraction showed trypanocidal activity with inhibition percent of 68.68. The activities of oxidative stress enzymes; superoxide dismutase (SOD) and catalase in the infected rats were determined. SOD activity was significantly higher than control (1.64 ± 0.026 I/U) in all fractions except ethyl acetate (1.56 ± 0.031 I/U). Catalase showed a significant decrease in activity in butanol (2.05 ± 0.015 I/U) and chloroform (2.18 ± 0.061 I/U) fractions compared to control (2.30 ± 0.015 I/U). Butanol fraction might have affected the redox equilibrium of the infected animals causing oxidative stress to the parasites. This is the basis of inhibition of growth of the parasites by the butanol fraction.