The purpose of this research was to evaluate the antiplasmodial activity of the aqueous fraction of the methanolic extract of Senna siamea at various dosage concentrations in vivo in experimental mice infected with chloroquine sensitive Plasmodium berghei NK65 strain. Groups A, B and C mice were infected and treated with 100, 200, and 300 mg extract/kg body weight of mouse respectively while group D was infected and treated with 200 mg chloroquine /kg body weight, group E was infected but not treated and group F was uninfected and untreated. The phytochemical constituents of the plant extract were evaluated giving 4 phytochemicals namely flavonoids and alkaloids, carbohydrates and saponins. In addition, the extract indicated a dose dependent decrease in the level of parasitaemia. The analysis showed that the extract has a decreasing effect on the Packed Cell Volume of the experimental mice. Also, some of the groups lived 10 days beyond the experimental period. Furthermore, the groups treated with 300 mg/kg extract, 200 m g/kg chloroquine and uninfected untreated increased in body weight compared to the negative control (infected untreated). Therefore, the aqueous fraction of the Methanol crude extract of Senna siamea leaves could serve as a possible source of antimalarial compounds.