It is difficult for anti-tuberculosis drugs to reach the tuberculous cavity lesions, and the effects of conventional oral or intravenous administration are not satisfactory. In this study, a rifapentine composite thermosensitive gel with poly (lactide-co-glycolide)-block-poly (ethylene glycol)-block-poly (lactide-co-glycolide) (PLGA-PEG-PLGA) as the gel matrix was developed for bronchoscopic pulmonary interventional therapy of pulmonary tuberculosis to enhance the targeted drug delivery treatment effect for pulmonary tuberculosis. An optimal formulation for rifapentine lipid microspheres was screened via orthogonal design. The lipid microspheres were then mixed with PLGA-PEG-PLGA solution to prepare a composite thermosensitive gel. The formulation was then characterized. The erosion of the in-situ gel was evaluated using a membrane-free method, while the in-vitro release and release mechanism were assessed by dialysis bag method. Uptake of the drug in the gel by A549 cells was observed using confocal microscopy. Antibacterial assays were assessed using lung tissue homogenates collected at various time points following a single administration, in order to investigate the pulmonary retention of the thermosensitive gel after intratracheal instillation in rats. All animal experimental procedures were approved by the Experimental Animal Ethics Committee of Hebei Medical University (No: IACUC-Hebmu-P 2022084) and carried out in accordance with its guidelines. The particle size of the prepared lipid microspheres was 482.4 ± 0.22 nm, which increased slightly after incorporation into the composite gel. The gelation temperature of the composite gel was 34.47 ± 0.15 ℃, with a gelation time of 41.33 ± 1.70 s. The formulation exhibited good injectability before gelation while showed a suitable viscosity at gelation temperature. The drug release model fitted with the Ritger-Peppas equation. The results of laser confocal microscopy showed that the lipid microspheres effectively delivered lipophilic drugs into lung epithelial cells. Antibacterial testing of lung tissue extracts confirmed that a single dose of the composite gel could sustain antibacterial activity in rat lungs for at least 14 days. The rifapentine lipid microsphere-thermosensitive gel composite formulation significantly enhances the solubility of rifapentine. Its temperature-dependent phase transition from liquid to gel not only ensures feasibility for bronchoscopic administration but also enables prolonged and effective drug release at the lesion site, thereby achieving the design goal of efficient local therapy for tuberculosis.