In this study we present pH-responsive rifampicin (RIF) microparticles comprising lecithin and a biodegradable hydrophobic polymer, polyethylene sebacate (PES), to achieve high intramacrophage delivery and enhanced antitubercular efficacy. PES and PES-lecithin combination microparticles (PL MPs) prepared by single step precipitation revealed average size of 1.5 to 2.7 µm, entrapment efficiency ∼ 60 %, drug loading 12–15 % and negative zeta potential. Increase in lecithin concentration enhanced hydrophilicity. PES MPs demonstrated faster release in simulated lung fluid pH 7.4, while lecithin MPs facilitated faster and concentration dependent release in acidic artificial lysosomal fluid (ALF) pH 4.5 due to swelling and destabilization confirmed by TEM. PES and PL (1:2) MPs exhibited comparable macrophage uptake which was ∼ 5-fold superior than free RIF, in the RAW 264.7 macrophage cells. Confocal microscopy depicted intensified accumulation of the MPs in the lysosomal compartment, with augmented release of coumarin dye from the PL MPs, confirming pH-triggered increased intracellular release. Although, PES MPs and PL (1:2) MPs displayed comparable and high macrophage uptake, antitubercular efficacy against macrophage internalised M. tuberculosis was significantly higher with PL (1:2) MPs. This suggested great promise of the pH-sensitive PL (1:2) MPs for enhanced antitubercular efficacy.