Abstract: This study aimed to investigate in vivo anti-malarial effect of methanolic extract of Cleome viscosa whole plant and fractions (n-hexane and ethyl acetate) against early, established and residual malaria infections. The in vivo anti-malarial effect against early infection, curative effect against established infection and prophylactic effect against residual infection were studied in chloroquine-sensitive Plasmodium berghei NK-65 strain infected mice. The results showed that the methanol extract of Cleome viscosa whole plant and partitioned fractions demonstrated significant (p<0.05) dose-dependent anti-malarial activity in all three antimalarial evaluation models thus justifying the inclusion of this plant in recipes for treating malaria.