BackgroundIn Tanzania and elsewhere, medicinal plants, including Maytenus senegalensis, are still widely used in the treatment of malaria and other ailments. The aim of the present study was to investigate the in vivo antiplasmodial and toxic effects in mice.MethodsOral antiplasmodial and acute toxicity of the ethanolic root extract of M. senegalensis was evaluated in mice. The Peters 4-day in vivo antiplasmodial effect against early rodent malaria infection in chloroquine-sensitive Plasmodium berghei NK 65 strain in mice.ResultsThe M. senegalensis extract was found non-toxic and the oral median lethal dose in mice was determined to be greater than 1,600 mg/kg body weight. The findings revealed a significant (P = 0.001) daily increase in the level of parasitaemia in the parasitized untreated groups and a significant (P < 0.001) dose dependent decrease in parasitaemia in the parasitized groups treated with varying doses ranging from 25 to 100 mg/kg body weight of M. senegalensis extract and the standard drug sulphadoxine/pyrimethamine at 25/1.25 mg/kg body weight. Overall, the dose dependent parasitaemia suppression effects were in the order of: 25/1.25 mg/kg body weight of sulphadoxine/pyrimethamine > 100 mg/kg > 75 mg/kg > 50 mg/kg > 25 mg/kg body weight of M. senegalensis extract.ConclusionThe implications of these findings is that M. senegalensis ethanolic root bark extract possess potent antiplasmodial effect and may, therefore, serve as potential sources of safe, effective and affordable anti-malarial drugs. The displayed high in vivo antiplasmodial activity and lack of toxic effect render M. senegalensis a candidate for the bioassay-guided isolation of compounds which could develop into new lead structures and candidates for drug development programmes against human malaria.