The major problems associated with the anti-tubercular (TB) drug therapy include loss of efficacy through bacterial resistance, side effects, low patient compliance and duration and complexity of treatment. The present study attempts to confront them through a combined approach consisting of microspheres and bioenhancers. Microspheres containing rifampicin were prepared by emulsification technique using stearic acid as a cross-linking agent. Extract of Carum carvi were added as a bioenhancer in variable amount of 5 to 15 mg for each dose of rifampicin. The loading efficiency and release behavior of loaded microparticles were found to be dependent on the cross-linker concentration, cross-linking time and drug-polymer ratio. Prolonged release of the drug from the microspheres was demonstrated in a simulated intestinal fluid. In-vitro release of rifampicin from the microspheres containing 15 mg of bioenhancer showed significant increase in release profile (87.42% in formulation containing bioenhancer against 51.41% for the formulation without bioenhancer) and the release rates were reduced upon increasing the amount of cross-liking agent and prolonging the cross-linking time.