The aim of the present study was to develop a novel long-acting Poly (lactic-co-glycolic acid) (PLGA)-based microspheres formulation of Bisdemethoxycurcum (BDMC) by emulsion-solvent evaporation method. Meanwhile, the effects of the volume ratio of the dispersed phase and continuous phase, the concentration of PLGA and PVA, the theoretical drug loading and stirring speed were investigated. The mean diameter of the microspheres was 8.5 µm and the size distribution was narrow. The encapsulation efficiency (EE) and drug loading efficiency (DLE) of BDME loaded PLGA microspheres (BDMC-PLGA-MS) was 94.18% and 8.14%, respectively. In an in vitro study of drug release, it can be concluded that the BDMC-PLGA-MS exhibited sustained and long-term release properties for 96 h. Stability studies suggested that the microspheres we prepared had a very good stability. Furthermore, the results of an in vivo study indicated that the BDMC-PLGA-MS had sustained release effect and was mainly distributed in the lung tissue, and less distribution in other tissues, which indicated that microspheres could be an effective parenteral carrier for the delivery of BDMC in lung cancer treatment.