The combination of isoniazid (INH) with troglitazone (Trog) additively facilitates Mycobacterium tuberculosis (Mtb) elimination in Mtb-infected mice. C57BL/6 mice were subjected to aerosol infection with approximately 200 colony-forming units (CFUs) of wild-type (WT) H37Rv or C2 per mouse. Drug administration began after 2 weeks of infection with continuous infusion for 2 weeks. The control group (negative control [NC]) was gavaged with 0.5% methylcellulose only, and the other groups were gavaged with 0.5% methylcellulose containing either Trog or INH alone or the combination of INH + Trog. Mice were euthanized at 1, 14, or 28 days. A, B, CFUs were enumerated in the lungs of the WT H37Rv-infected (A) and C2-infected (B) mice (n = 6). C, Mtb-infected lungs were stained with hematoxylin-eosin 28 days after infection. One representative image is shown (scale bars, 200 µm). D, In WT H37Rv-infected lungs, immunofluorescent staining with the indicated antibodies was performed 28 days after infection. One representative image is shown (scale bars, 200 or 100 µm), along with quantitative analysis of the mean fluorescence intensity (MFI) of microtubule-associated protein 1 light chain 3B (LC3B) in CD68⁺ cells in the lungs. Abbreviations: DAPI, 4',6-diamidino-2-phenylindole; DMSO, dimethyl sulfoxide; FITC, fluorescein isothiocyanate. Data are presented as means with SDs (n = 6). Statistical analysis was performed using 1-way analysis of variance, followed by Tukey test (A, B, D). *P < .05; **P < .01; ***P < .001; NS, not significant.