Abstract: Alstonia boonei De Wild is a medicinal plant used widely in Nigeria for the management of malaria and other ailments. The aim of the present study was to investigate in vivo antiplasmodial effect in mice. Oral acute toxicity of the ethanolic stem bark extract of Alstonia boonei was evaluated in mice using modified Lorke’s method and the in vivo anti-plasmodial effect against early infection, curative effect against established infection and prophylactic effect against residual infection were studied in chloroquine-sensitive Plasmodium berghei berghei NK65-infected mice. The oral median lethal dose of the extract in mice was determined to be greater than 5000 mg kg-1 body weight. The extract at all the doses (100, 200 and 400 mg kg-1, p.o.) used, produced significant (p<0.05), dose-dependent activity against the parasite in the suppressive, curative and prophylactic tests. These results showed that Alstonia boonei ethanolic stem bark extract possesses potent antimalarial effects and may therefore offer the potential for a safe, effective and affordable antimalarial phytomedicine.