A polymeric prodrug, PEGylated indomethacin (MPEG-indo), was prepared and then used to interact with alpha-cyclodextrin (alpha-CD) in their aqueous mixed system. This process could lead to the formation of supramolecular hydrogel under mild conditions and simultaneous encapsulation of MPEG-indo in the hydrogel matrix. For the formed supramolecular hydrogel, its gelation kinetics, mechanical shear thinning behavior and thixotropic response were investigated with respect to the effects of MPEG-indo and alpha-CD amounts by dynamic and steady rheological tests. Meanwhile, the possibility of using this hydrogel matrix as injectable drug delivery system was also explored. By in vitro release and cell viability tests, it was found that the encapsulated MPEG-indo could exhibit a controlled and sustained release behavior as well as maintain its biological activity. P