Aims: To evaluate the antimalarial activity of the aqueous (KGA) and n-hexane (KGN) extracts of the stem bark of Khaya grandifoliola (Meliaceae) in combination with artemisinin (ART) in mice. Study Design: Preclinical antimalarial assessment in mice subjects. Place and Duration of Study: Biological Laboratory, Drug Research and Production Unit, Obafemi Awolowo University, Ile-Ife between November 2006 and September 2007. Methodology: In the first phase, 65 mice inoculated intraperitoneally with Plasmodium berghei were divided into groups of five mice each. Oral administration of KGA and KGN (50-400 mg/kg each) and artemisinin (0.2-1.6 mg/kg) was done for four days starting on the day of inoculation in the 4-day antimalarial test model. Giemsa-stained thin blood smear, from the tail of each mouse, was microscopically assessed for the parasitized and total number of red blood cells of ten fields. The combinations of the sub - effective doses of each of KGA and KGN (100 mg/kg) with ART (0.2 mg/kg) were similarly evaluated and assessed. Results: The median effective doses (ED50) were 0.29, 140 and 160 mg/kg for Artemisinin, KGA and KGN, respectively. The combinations (KGA: ART and KGN: ART) resulted in improved parasitemia suppression which were statistically significant (P = .05) when compared with the percentage parasitaemia obtained for individual agents of the combinations. Conclusion: Extracts of K. grandifoliola potentiated the antimalarial activity of Artemisinin. The results showed beneficial interaction with potentials in antimalarial combination therapy.