The efficient synthesis of codendrimer PAMAM-co-OEG (PAG) and its properties in aqueous solution, including particle size and thermosensitivity, are described. PAG is synthesized with well-defined structure through the "attach to" route. In the aqueous solutions, PAG forms unimer and multimolecular aggregates with the respective particle sizes of approximately 8 and 200 nm, depending on the concentration. PAG shows thermosensitive behavior with sharp and fast transition, and the lower critical solution temperature is 38.2 °C. The suitability of codendrimer PAG as the thermosensitive carrier is evaluated with methotrexate (MTX) as the model drug. MTX is encapsulated in PAG with the drug-loading capacity of 39%, among which 30% of MTX is encapsulated in PAMAM core. The release behavior of MTX mediated by temperature is investigated with focus on the effects around the LCST of PAG.