Malaria is a major health problem that still affects numerous countries. The current study aimed to identify the role of leaf extract in regulating mouse spleen macrophages during the progression of infection. Three doses of the leaf extract (100, 200, and 300 mg/kg) were administered to mice inoculated with infected erythrocytes. The weight of the infected mice improved after the treatment with . The infection causes disorganization of macrophage distribution in the spleen. After the mice had been treated with the leaf extract, the macrophages appeared to be reorganized in the white and red pulp areas. In addition, the leaf extract (IOLE) significantly increased the total antioxidant capacity of the mice spleens infected with . The phagocytic activity of spleen macrophages was increased in the infected group as indicated by the significant decrease in the number of fluorescent particles in the spleen sections. This number increased in the mice spleens after treatment with IOLE. Based on these results, it is suggested that IOLE regulate macrophage response of the spleen during the blood stage of malaria in mice.