The vertebrate reticuloendothelial system (RES) functions to remove potentially damaging macromolecules, such as excess hormones, immune-peptides and -complexes, bacterial-endotoxins, microorganisms and tumor cells. Insect hemocytes and nephrocytes - which include pericardial cells (PCs) and garland cells - are thought to be functionally equivalent to the RES. Although the ability of both vertebrate scavenger endothelial cells (SECs) and PCs to sequester colloidal and soluble macromolecules has been demonstrated the molecular mechanism of this function remains to be investigated. We report here the functional characterization of Drosophila larval PCs with important insights into their cellular uptake pathways. We demonstrate the nephrocyte function of PCs in live animals. We also develop and use live-cell assays to show that PCs take up soluble macromolecules in a Dynamin-dependent manner and colloids by a Dynamin-independent pathway. We had earlier identified Drosophila rudhira (Drudh) as a specific marker for PCs. Using RNAi mediated knock-down we show that Drudh regulates macropinocytic uptake in PCs. Our study establishes important functions for Drosophila PCs, describes methods to identify and study them, provides a genetic handle for further investigation of their role in maintaining homeostasis and demonstrates that they perform key subsets of the roles played by the vertebrate RES.