Depletion of splenic and hepatic macrophages has potentials to alleviate hemorrhage in patients who suffered from immune thrombocytopenic purpura (ITP). This investigation was aimed to assess whether nanotechnology can play a role in this clinical setting by absorbing bisphosphonate clodronate (CLOD) to type A gelatin nanospheres (GNS) to form CLOD–GNS. First, the stability of CLOD–GNS was assessed in vitro and up to 6 mg CLOD can be adsorbed in 1 mg GNS. The ability of CLOD–GNS to target the spleen and the liver was then evaluated by biodistribution assay and 99mTc–CLOD–GNS scintigraphy in rats. It showed that up to 70.6% of CLOD–GNS could be accumulated in the liver and spleen. The survival of the macrophages in vitro and the phagocytic ability of hepatic and splenic macrophage in vivo were reduced and later demonstrated by 99mTc-phytic colloid scintigraphy. In rats with induced ITP, administration of CLOD–GNS successfully prevented peripheral platelet levels from decreasing. Our preliminary data demonstrate that CLOD–GNS can effectively target reticuloendothelial system and its potentials in the treatment of ITP warrants further study.