Iron overload (IO) because of multiple blood transfusion as a definite therapy for hematological disease with chronic and severe anemia has become a major concern. Deleterious complication contributed by chemically reactive deregulated iron may affect cellular homeostasis systemically lead to tissue and organ damage. When this toxicity occurred in blood cells, alteration of peripheral hematological profile concerning erythrocyte, leucocyte, and platelet most likely to be modified and imperatively need to be evidenced. Theexperimental IO mice model was established by injecting a low and high dose of iron dextran intraperitoneally. Peripheral erythrocyte, leucocyte and platelet indices measured by hematology analyzer were analyzed. A dynamic tendency of leucocyte absolute cell number and differential cell count of low and high dose iron treatment and a significant decrease of differential monocyte count were found. In addition, high dose iron treatment showed a significantly lower mean platelet volume. In conclusion, this study verified that IO impaired the cellular hematological indices by selectively suppress monocyte number addressing that this mononuclear phagocyte was the most affected immune cell. Furthermore, low mean platelet volume following acquired platelet function defect was evidenced. This research provided an animal experimental model that could be used for further study in finding alternative therapeutic targets on the pathophysiology of iron overload diseases, such as thalassemia.