Abstract In sarcoidosis, a chronic granulomatous disease of unknown etiology, alveolar macrophages are deficient in the nuclear transcription factor peroxisome proliferator-activated receptor gamma (PPARγ). Pulmonary fibrosis may accompany sarcoidosis and increase morbidity and mortality. We developed a murine model of granulomatous disease elicited by instillation of multiwall carbon nanotubes (MWCNT) and reported increased granulomas in macrophage-specific PPARγ KO mice compared to wild type mice. Because mycobacterial antigens can associate with sarcoidosis, we hypothesized that both T effector cells and pulmonary fibrosis may be exacerbated by PPARγ deficiency and exposure to Mycobacterial Early Secreted Antigenic Target Protein 6 (ESAT-6). Modified Ashcroft scoring of Trichrome staining indicated increased pulmonary fibrosis in mice receiving MWCNT + ESAT-6 compared to MWCNT alone. No changes occurred with PBS or ESAT-6. Analysis of mediastinal lymph nodes revealed increased frequency and number of Th1 cells with corresponding reductions in Th2 cells in PPARγ KO mice after MWCNT, compared to wild-type controls. Notably, the number of Th1, Th2 and Th17 cells were each increased in PPARγ KO after MWCNT + ESAT-6 compared to after administration of MWCNT alone. Our findings suggest that: (1) PPARγ deficiency exacerbates Th1 activation and pulmonary fibrogenic pathways; and (2) the murine MWCNT model may offer novel insights into fibrotic transformation and possible therapeutic options.