The crude methanol extracts of leaf, stem bark, root bark and stem bark fractions of Trichilia megalantha (Meliaceae) were screened for in vivo antimalarial activities in mice against a chloroquine resistant Plasmodium berghei berghei ANKA clone using the 4-day suppressive test procedure. Chloroquine diphosphate was used as the positive control. The extracts demonstrated intrinsic antimalarial property. Of all the seven extracts studied, the stem bark gave the highest activity. At 200 mg/kg of mouse, the stem bark extract had complete suppression of parasite growth (100%). Least activity was observed for the leaf extract, while the root bark had a parasite suppression of 98.4% at 800 mg/kg comparable to that of Chloroquine. Percentage suppression of parasite growth on day 4 post-infection ranged from 3.1 to 96.1% in mice infected with P. berghei and treated with extracts and fractions of T. megalantha when compared with chloroquine diphosphate, the standard reference drug which had a chemosuppression of 96.2%. At 400 mg/kg, the stem bark chloroform fraction was the most active fraction with 89.1% parasite growth suppression followed by the ethyl acetate fraction (76.4%), hexane soluble fraction (54.8%) and methanol fraction (20.5%). The mean survival time of mice that received extract ranged from 8.75 ± 0.65 to 26.0 ± 1.2 days (increased as the dose increases to 800 mg/kg), which was statistically significant, except the lowest dose (100 mg/kg) compared to the negative control group mice (9.45 ± 0.6 days). The animals that were treated with Chloroquine had mean survival time of 23.5 ± 1.2 days.