Abstract: Objective To explore whether Cl2MDP-loaded gelatin particles can induce the depletion of macrophage or can depress the immunity of macrophage in SD rat models of immune thrombocytopenic purpura (ITP) to treat the ITP rats. Methods SD rats were intravenously injected with 150 μl of anti-platelet serum once per 24 hr to induce the ITP model. The platelet counts were persistently less than 50×109/L in these models. After intravenous injection of a group dose of Cl2MDP-gelatin particles, the platelet counts of these models were examined at the time of 4 hr, 24 hr, 48 hr, 72 hr and 96 hr, respectively. The pathological changes of macrophages in spleen were observed by electron microscope. Results Cl2MDP-loaded gelatin particles can increase significantly the platelet counts of ITP models from less than 50×109/L to mean 180×109/L in 24 hr after injection, and can keep the platelet level through whole experimenting process. The pathological changes of macrophages were seen under electron microscope, such as degeneration, necrosis and so on. Furthermore, rats that were pre-treated with Cl2MDP-loaded gelatin particles can evade the decrease of platelet counts when they were injected anti-platelet serum. Conclusion Cl2MDP-loaded gelatin particles can promptly, effectively restore platelet counts of ITP models to physiologically level, in a dose dependent manner. So, the targeting therapy of drug-loaded gelatin particles offers a new approach to treat ITP, and this strategy is worthy of further studies.