Drug delivery into immune cells has high potential for the treatment of all kinds of inflammation, allowing a target-oriented transport of active agents. The advantage of this local drug release is the prevention of negative effects of systemic applications and low-dose application. Thereby, the phagocytotic capability of mature phagocytes is essential. Microparticles can be loaded with immune regulatory substances to control and terminate inflammatory processes. In this study, silica microparticles were co-incubated with monocyte/macrophage-like cells in order to determine phagocytotic particle uptake. The phorbol ester-triggered differentiation was proven by the increased expression of surface markers as phosphatidylserine and CD14 and enhanced lysosomal activity. Particle/cell co-incubation results in cell surface attachment followed by phagocytosis. Phagolysosomal ingestion could be determined by co-localization using fluorescence staining techniques. In contrast, no particle interaction with undifferentiated cells could be found. Under phagolysosomal conditions, multilayer degradation within 22 h could be shown, indicating a valuable carrier basis design for the time-controlled delivery of active agents. Subsequently, it can be assumed that a higher differentiation degree allows phagocytosis of microparticles, providing drug delivery into immuno-active cells.