A novel amphiphilic copolymer of hyperbranched polyesteramides-graft-mono methoxy polyethylene glycol (HP-g-MPEG) was synthesized by solution polymerization in ethyl acetate using 2,4-tolylene diisocyanate (TDI) as a coupling agent. The copolymers were prepared by two-step reactions. First, the isocyanate-terminated intermediate (MPEG-NCO) was prepared by introducing one NCO group of TDI onto the hydroxyl end-group of mono methoxy polyethylene glycol (MPEG). Second, MPEG-NCO was grafted onto the chains of hyperbranched polyesteramides (HP) by the reaction between the unreacted NCO group and the hydroxyls of HP, and then, HP-g-MPEG was obtained. The chemical structure of HP-g-MPEG was confirmed by FT-IR and H-1 NMR.