Rifabutin is broad spectrum antimicrobial drug, used for the treatment of infection caused by M. tuberculosis, M. avium and M. Leprae and also used in the treatment of multidrug resistant TB. Rifabutin is poorly water soluble drug (0.19mg/ml) with high permeability. In the present study, Rifabutin Liquisolid system were prepared using mixed solvency concept for the improvement of solubility and dissolution rate that improve drug release and oral bioavailability. Different blends were prepared using various solid solubilizers like sodium benzoate, sodium caprylate and niacinamide in propylene glycol (co-solvent). In this blend K (35%SC+5%NM+5%SB) gives highest solubility and selected for further study. Liquisolid system was prepared using blend K, microcrystalline cellulose as carrier material and aerosil as coating material. In all the formulations, formulation LSS-01 was selected as best formulation as it released 98.20% of drug in 1 hrs. The prepared Liquisolid system (LSS-01) using mixed solvency concept was evaluated for Drug content, X-RD analysis, dissolution study and stability study. Drug content in LSS-01 was found to be 100.24± 0.04% & in Physical mixture was found to be 98.9± 0.03%. X-ray diffraction study showed that the crystallinity of drug is not much reduced. Drug release profile of optimized batch LSS-01 showed enhanced dissolution behavior (98%in60min.)ascomparetopuredrug(46.26±0.011),physicalmixture(51.42±0.006)andmarketedformulation(48.92±0.009).