Macrophages eliminate and destroy invading bacteria and contaminants by engulfing them or secreting cytokines that trigger downstream immune responses. Consequently, impairment of the phagocytic functions of macrophages and/or suppressing their cytokine secretion are dangerous to organisms that rely on immune protection. Accordingly, exposure to environmental nanoparticles (NPs) that display immunomodulatory properties are serious. In this work, two types of NPs, i.e., mild-toxicity CuInS2 NPs and high-toxicity CdTe NPs, were used to evaluate the effects of NP exposure for macrophages. Following incubation for 24 h, THP-1-derived macrophage viability was assessed using an MTT method after exposing the THP-1 cells to different concentrations of CuInS2 or CdTe NPs. Phagocytosis assays demonstrated that both CuInS2 and CdTe NPs impair phagocytic activity toward Staphylococcus aureus (S. aureus). After pretreatment with CuInS2 and CdTe NPs at 4 mu mol/L, THP-1 macrophages exhibited decreases in phagocytic ratio from ca. 32.9% to ca. 18.5% and 18.7%, respectively. Since the zeta potentials of intact and weathered CuInS2 NPs were distributed over a wide range from positive to negative, large quantities of intact and weathered CuInS2 NPs bore sufficient positive charge on their surfaces to induce membrane depolarization, thus theoretically providing electrostatic forces between S. aureus and THP-1, which could induce downstream intracellular events that increase phagocytosis. However, real time polyrnerase chain reaction arrays revealed that transcription of the pro-inflammatory factors IL-1 beta, IL-6, and TNF-alpha decreased while that of the anti-inflammatory factor IL-10 increased after treatment with CuInS2 NPs. Furthermore, transcription of TNF-alpha decreased while IL-10 increased after treatment with CdTe NPs. Thus, both kinds of NPs inhibited phagocytosis of S. aureus by THP-1 to some extent, confirming that immunosuppression can occur when macrophages are exposed to environmental NPs.