This study investigated the effects of cadmium (Cd) and monensin on spleen function in mice, subjected to subacute Cd-intoxication. Adult male ICR mice were divided into three groups (n = 6 per group) as follows: control group (received distilled water and food ad libitum); Cd-treated (20 mg/kg/b.w./day Cd(II) acetate for the first 2 weeks of the experimental protocol); monensin-treated mice (20 mg/kg/day Cd(II) acetate for the first 2 weeks followed by treatment with 16 mg/kg b.w./day monensin from days 15 to 28. On day 29, mice were sacrificed under light ether anesthesia. Exposure to Cd induced an increase in spleen index (SI). The treatment of cd-intoxicated mice with monensin significantly reduced SI compared to Cd alone. The data from the atomic absorbption analysis of spleen revealed a significant Cd accumulation in Cd-treated mice compared to controls, accompanied by a significant depletion of Fe concentration up to 30%. The treatment of the Cd-administered mice with monensin resulted in a significant decrease of Cd in spleen by 50% compared to Cd alone. Fe recovery occured in spleen of monensin-treated mice. Histopathological analysis of spleen showed that Cd significantly decreased the number of megakaryocytes and disturbed extramedullary hematopoiesis. The number of megakaryocytes increased when monensin was added. The data in this study suggest that monensin was able to reduce the effects of Cd on hematopoesis in mice.