A water-soluble cationic dendrimer with a central fluorescent perylenediimide (PDI) chromophore and many peripheral amines can rapidly penetrate into live hemocytes, gut and fat body. By double fluorescence tracing, the dendrimer is demonstrated to have a high gene-transfection capacity. The synthesized dsRNA targeting at serpin-3, a key immune gene, is systemically delivered by the dendrimer to insect fat bodies and hemocytes outside of midgut. Biological assays, including PCR and immunoblotting, show that the expressions of the target gene and its downstream immunity-related genes are largely suppressed. This study demonstrates for the first time that a PDI-cored, cationic, dendrimer-mediated dsRNA systemically interferes with the immune response in insects. This work provides an insect model for immunology research and a novel strategy for potential pest control.