A novel polymerization methodology for efficient synthesis of hyperbranched polyethylene amphiphiles by chain walking polymerization (CWP) followed by RAFT polymerization has been developed. Hyperbranched polyethylene with hydroxyl ends (HBPE-OHs) is first synthesized via chain walking copolymerization of ethylene with 2-hydroxyethyl acrylate with Pd-α-diimine catalyst. The hydroxyl groups of hyperbranched polyethylene are then converted into thiocarbonyl thio moieties by an esterification reaction with trithiocarbonate 3-benzylsulfanylthiocarbonyl sulfanylpropionic acid (BSPA). The hyperbranched polyethylene with thiocarbonyl thio moiety ends (HBPE-BSPAs) is used as a macro-RAFT agent for the synthesis of hyperbranched polyethylene amphiphiles, HBPE-PDMAEMAs, by RAFT polymerization of N,N-dimethylaminoethyl methacrylate (DMAEMA). The resultant HBPE-PDMAEMAs can self-assemble to form supramolecular polymer vesicles in aqueous solution. A preliminary investigation on thermo- and pH-responsive behaviors of the polymer is also reported.