Cancer is a group of diseases in which normal cells are converted to cells capable of autonomous growthand invasion. In the chemotherapeutic control of cancer, drugs are usually given systemically so they reachtoxic levels in cancer cells. This causes serious side effects in healthy cells. Another important problem withchemotherapy is resistance developed to cytotoxic drugs (multi drug resistance). As a possible solution tothese problems, in the present study, two different microparticle fabrication methods were compared; doubleemulsion solvent evaporation (SE) method for encapsulation of Doxorubicin into PLGA microparticles.The most appropriate method was the SE techniquies which lead to higher encapsulation efficiencies.Processing factors were evaluated for their effects on encapsulation efficiency and results indicated thatany change that hinder drug diffusion would result in increased drug content in microparticles. To assesthe cytotoxicities of synthesized microparticles, cell proliferation assays were performed with XTT reagenton Doxorubicin resitant and sensitive breast cancer cell lines, MCF-7. DOX entrapped microparticles waseffective on both sensitive and DOX resistant MCF-7 cells. The concentration of drug in resistant cancercells was increased indicating a partial reversal of drug resistance. The results of this study will providenew insights to the development of new drug delivery systems for cancer therapy.