Tuberculosis (TB) is a common disease caused by Mycobacterium tuberculosis (M.tb) infection. Our study was to explore the function and mechanism of circular RNA WD repeat domain 27 (circ-WDR27) in TB progression. Cell viability and apoptosis were detected by 3-(4, 5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide assay and flow cytometry. Protein quantification was performed by Western blot. Inflammatory cytokines were examined using enzyme-linked immunosorbent assay. RNA levels were assayed via quantitative reverse-transcription polymerase chain reaction. M.tb survival was assessed using colony-forming unit assay. Target binding was analyzed via dual-luciferase reporter assay and RNA immunoprecipitation assay. Cell damages were induced by M.tb infection, and inflammatory cytokines were secreted in human macrophages. Circ-WDR27 was downregulated in TB patients and M.tb-infected macrophages. Circ-WDR27 overexpression reduced M.tb survival and released inflammatory cytokines in macrophages. Circ-WDR27 acted as a sponge for miR-370-3p. Circ-WDR27-mediated inhibition of TB progression was partly achieved by sponging miR-370-3p. miR-370-3p directly targeted Follistatin-like protein 1 (FSTL1). FSTL1 suppressed M.tb-induced cell damages, and reversed the protective role of miR-370-3p inhibition in TB progression. Circ- WDR27 regulated FSTL1 expression by targeting miR-370-3p. These results showed that circ-WDR27 repressed M.tb vitality and stimulated pro-inflammatory cytokines in M.tb-infected macrophages by affecting the miR-370-3p/FSTL1 axis.