Two-dimensional electrophoresis (2-DE) was employed to compare the global protein patterns between human macrophage cell line U937 infected and that uninfected with Mycobacterium tuberculosis (MTB) isoniazid (INH) resistant strains, and 32 protein spots were found to express differentially. Five protein spots which remarkably increased in U937 infected with MTB INH-resistant strains were measured by matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS). The data obtained from peptide mass fingerprinting were used in protein database search. Five protein spots in gel were identified as HSP105_β, inhibitor of apoptosis protein-1, phosphoglycerate mutase 1, cathepsin B, desmocollin 3. These data provide insight into the changed global protein patterns of the U937 while in stasis shortly after infection and may prove useful for further study in the interaction between MTB INH-resistant strains and host.