We developed a target drug delivery system for the treatment of tuberculosis using rifampicin (RIF) incorporated into hyaluronic acid-tocopherol succinate (HA-TS) micelles. The RIF-HA-TS micelles were physicochemically characterized and the cellular uptake of RIF-HA-TS micelles on murine alveolar macrophage MH-S cells was investigated. Furthermore, the cytokine secreting activities of the alveolar macrophages after treatment with RIF-HA-TS micelles were evaluated. The results of the studies indicate that (i) mean particle size of HA-TS micelles was in the range of 212-294.6 nm depending on the degree of substitution (DS) of the hydrophobic moiety. The incorporated RIF was sustained released from RIF loaded HA-TS micelles (ii) cellular uptake of RIF-HA-TS micelles was dose and energy dependent (iii) RIF-HA-TS micelles had a significant uptake in comparison to free RIF, with the highest uptake at 12 h (iv) RIF-HA-TS micelles were taken up into cells via phygocytosis as well as CD44 receptor-mediate endocytosis (v) beside E. coli lipopolysccharide (LPS), HA-TS micelles also could activate MH-S cells, which improved the RIF-HA-TS uptake (vi) RIF-HA-TS micelles induced higher concentration of Th1 cytokines than free drug, which will help to enhance the anti-tuberculosis activity. The results of the current studies demonstrate the feasibility of targeting macrophages and the possibility of using the HA-TS micelles for tuberculosis treatment.