Objective:To investigate the antiplasmodial activity of the extracts ofPhyllanthus amarus (P. amarus) onPlasmodium yoelii (P. yoelii) (a resistant malaria parasite strain used in animal studies) infection in mice.Methods: The aqueous and ethanol extracts of the whole plant of Phyllanthus amarus was administered to Swiss albino mice at doses of200 mg/kg/day,400 mg/kg/day,800 mg/kg/day and1 600 mg/kg/day and the prophylactic and chemotherapeutic effect of the extracts againstP. yoelii infection in mice was investigated and compared with those of standard antimalaria drugs used in the treatment of malaria parasite infection. Acute toxicity test was carried out in mice to determine the safety of the plant extract when administered orally. Results: The results showed that the extracts demonstrated a dose-dependent prophylactic and chemotherapeutic activity with the aqueous extracts showing slightly higher effect than the ethanol extract. The antiplasmodial effects of the extracts were comparable to the standard prophylactic and chemotherapeutic drugs used in chloroquine resistantPlasmodium infection although the activity depended on the dose of the extract administered. The extracts showed prophylactic effect by significantly delaying the onset of infection with the suppression of79%at a dose of 1 600mg/kg/day.Conclusions: The results obtained indicate that the extracts of the whole plant ofP. amaruspossess repository and chemotherapeutic effects against resistant strains ofP. yoelii in Swiss albino mice. The findings justify the use of the extract ofP. amarus in traditional medicine practice, for the treatment of malaria infections.