Inhalable clofazimine-containing dry powder microparticles (CFM-DPI) and native clofazimine (CFM) were evaluated for activity against Mycobacterium tuberculosis in human monocyte-derived macrophage cultures and in mice infected with a low-dose aerosol. Both formulations resulted in 99% killing at 2.5 g/ml in vitro. In mice, 480 g and 720 g CFM-DPI inhaled twice per week over 4 weeks reduced numbers of CFU in the lung by as much as log10 2.6; 500 g oral CFM achieved a log10 0.7 reduction.