Objective:To examine the in vitro and in vivo anti-Trypanosoma evansi (T. evansi ) activity of saponins-rich fraction of Calotropis procera (cpsf) leaves as well as the effect of the fraction on the parasite-induced anemia. Methods:A 60-minutes time course experiment was conducted with various concentrations of the fraction using a 96-well microtiter plate technique, and subsequently used to treat experimentally T. evansi infected rats at 100 and 200 mg/kg body weight. Index of anemia was analyzed in all animals during the experiment. Results:The cpsf did not demonstrate an in vitro antitrypanosomal activity. Further, the cpsf treatments did not significantly (P>0.05) keep the parasites lower than the infected untreated groups. At the end of the experiment, all T. evansi infected rats developed anemia whose severity was not significantly (P>0.05) ameliorated by the cpsf treatment. Conclusions:It was concluded that saponins derived from Calotropis procera leaves could not elicit in vitro and in vivo activities against T. evansi.