AbstractLipofundin is the solvent for propofol in the intravenous injection of Propofol‐Lipuro® and is used in patients who need intravenous feeding to provide fatty acids and fat for energy. In addition to propofol, Lipofundin also affects the immune modulation of phagocytes. In a previous study, we reported that intravenous propofol effectively decreased Staphylococcus aureus‐stimulated reactive oxygen species (ROS) levels, IL‐1β secretion, and phagocytosis in RAW264.7 macrophages. It is important to separately assess the effects of pure propofol, Lipofundin, and Propofol‐Lipuro. By using an S. aureus‐infected RAW264.7 macrophage model, the levels of secreted IL‐1β in cell supernatants were determined by ELISA. IL‐1β mRNA in cell pellets was further analyzed by quantitative polymerase chain reaction (qPCR), and Western blotting was performed to detect pro‐IL‐1β synthesis. Total ROS levels were determined by a luminol chemiluminescence assay. Compared with pure propofol, treatment with clinically relevant concentrations of Propofol‐Lipuro and Lipofundin obviously reduced IL‐1β secretion (>85% inhibition), S. aureus‐stimulated ROS production (50% inhibition), and phagocytosis (>60% inhibition) to similar levels. Treatment with pure propofol alone significantly decreased IL‐1β mRNA levels and pro‐IL‐1β protein synthesis, and slightly inhibited phagocytosis. In contrast, treatment with Propofol‐Lipuro did not influence IL‐1β mRNA or pro‐IL‐1β protein expression, even though treatment with Lipofundin increased the levels of both IL‐1β mRNA and its precursor protein. In conclusion, IL‐1β secretion is regulated at the posttranslational level. Lipofundin mediated the major effect of Propofol‐Lipuro on the inhibition of IL‐1β secretion, ROS production, and phagocytosis in S. aureus‐infected RAW264.7 cells.