TMT-based quantitative proteomic profiling was performed in RAW264.7 macrophages under control, LPS-stimulated, and additional experimental conditions. For the LPS group, cells were stimulated with 500 ng/mL LPS for 24 h. Three biological replicates were included for the control and LPS groups. The dataset contains raw mass spectrometry files, peptide- and protein-level identification results, the protein sequence database used for searching, and experimental design information. The control and LPS groups were used in the associated study to characterize proteomic alterations in inflammatory macrophages.