Abstract: Pluronic modified polyamidoamine (PAMAM) conjugate (PF127-PAMAM) was prepared and the inhibiting effect of MDR against MCF-7/ADR was investigated with doxorubicin (DOX) as model drug. ¹H NMR and FTIR spectra showed that the conjugate was synthesized successfully. Element analysis accu-rately measured that 27.63% amino of per PAMAM was modified by pluronic (PAMAM:PF127, 1:35.37 mole ratio). PF127-PAMAM showed an increased size and a reduced zeta potential compared to PAMAM. PF127-PAMAM had lower hemolytic toxicity and cytotoxicity due to the reduced zeta potential and the protection of PF127. Each PF127-PAMAM molecular could load 19.58 DOX molecules, and the complex exhibited sustained and pH-sensitive release behavior. PF127-PAMAM/DOX exhibited weaker cytotoxicity than free DOX in MCF-7 cells; while the complex showed much stronger reverse effect of drug resistance in MCF-7/ADR cells, and resistance reversion index (RRI) was as high as 33.15.