This study is devoted to developing amphiphilic, biodegradable, Y-shaped block polymers, which can self-assemble to form nanoparticles, as a glucose-sensitive drug carrier. Y-shaped poly(ethylene glycol)-block -[poly(lactic acid)-block -poly (2-phenylborate esters-1,3-dioxane-5-methyl) methylacrylate)] 2 (MPEG-(PLA-block -PPBDMMA) 2 ) polymers are constructed via a combination of ring-opening polymerization (ROP) and atom transfer radical polymerization (ATRP) with MPEG-(OH) 2 , having double initiation endings, as starting material. These Y-shaped block polymers can disperse in an aqueous medium and self-assemble into micellar aggregates with a spherical core-shell structure. Dynamic laser scattering (DLS), zeta potential measurements, and transmission electron microscopy (TEM) show the solution properties of these polymeric micelles with or without insulin loading. Compared with MPEG-PLA-block -PPBDMMA linear polymer, in vitro insulin release at different glucose concentrations, revealed by the fl uorescence technique, shows that the studied Y-shaped polymers have intelligent glucoseconcentration-dependent manner of insulin release at pH 7.4 and 37 °C. The bulk swelling phenomenon of the polymeric micelles formed from the Y-shaped polymers is detected by DLS in the process of their glucose-responsiveness. Such a Y-shaped glucose-responsive polymer is a promising candidate that holds great potential in the treatment of diabetes. predicted to drastic increase to 440 million by 2030, [ 1 ] and it has become one of the most important health concerns we ought to confront. Currently, the common treatment involves frequent blood glucose monitoring and multi ple daily insulin injections. [ 2 ] This provides some control of the diabetic state, but this is far from the physiologic regulation achieved by a normally functioning pancreas and results in unexpected fl uctuations in blood glucose and long-term complications. [ 3,4 ] Great effort has been 0 1 0 2 0 3 0 4 0 5 0 0 20 40 60 80 100 Cumulative Release % Time (h) [Glc]= 0 mg/mL [Glc]=1.0 mg/mL [Glc]=3.0 mg/mL [Glc]=5.0 mg/mL