Amphiphilic diblock copolymer was synthesized in one-step or two-step process by using of methoxy polyethylene glycol (MePEG), 1,6-hexanediol and maleic anhydride and characterized by FTIR and GPC. IR spectrum of amphiphilic diblock copolymer confirmed that MePEG had grafted on polyester. Solution polycondensation, melt polycondensation, mode of adding monomers and reaction time were studied on effect of molecular weight and its distribution. The GPC results showed that fairly narrow molecular weight distribution was obtained in solution polycondensation by one-step process. In addition, self-assemble behavior of amphiphilic diblock copolymer was discussed in different solvents by nanoprecipitation technique. The micelle size and aggregation was measured by TEM. It was found that MePEG1900-b-Polyester2162 copolymer self-assembled in acetone solution against water into well core-shell nanoparticles.