Abstract: OBJECTIVE To improve the treatment efficacy of doxorubicin to human breast cancer drug-resistant MCF-7/ADR cells, the synthesis of Poloxamer 188-PLGA conjugates and preparation of doxorubicin-loaded Poloxamer188 modified PLGA nanoparticles were investiagated. METHODS Poloxamer 188-PLGA was synthesized by using EDC/NHS, and the product was confirmed by nuclear magnetic resonance(NMR) and its critical micelle concentration was measured. Doxorubicin-loaded nanoparticles were prepared by the nanoprecipitation method, and the particle size was analyzed by laser scattering particle counter. Cellular uptake was observed using a fluorescence microscope and cell viability was determined by MTT assay. RESULTS Poloxamer 188-PLGA was synthesized successfully, and the average size of doxorubicin-loaded nanoparticles was about 140 nm. The nanoparticles could improve the intracellular delivery of doxorubicin and thus enhance the cytotoxicity in MCF-7/ADR cells. CONCLUSION Poloxamer 188 modified PLGA nanoparticles can reverse drug resistance and increase the cytotoxicity of doxorubicin in MCF-7/ADR cells.