A novel pH-sensitive carboxymethyl chitosan graft polyacrylic acid(CMC-g-PAA) hydrogel is fabricated via a free radical heat-initiated graft copolymerization reaction with acrylic acid(AA) and carboxymethyl chitosan(CMC) as monomers. The polymerization is successful, which is confirmed via fourier transform infrared spectroscopy (FT-IR). The result of swelling experiment indicates that the final CMC-g-PAA hydrogel has significant pH-sensitivity. Insulin(INS), as a model drug, is loaded into the hydrogel and 216.5 mg/g incorporation of INS is obtained. In vitro release profiles suggest that INS release is (16.3±2.6)% when pH is 1.2 after 2 h. INS release is (57.2±3.5)% in PBS with pH of 7.4 after the next 2 h. The study indicates that the CMC-g-PAA hydrogel loaded with INS could targeted deliver INS in intestinal, and avoid that INS is destroyed by gastric acid and pepsin. The experiment result on animals indicates that the CMC-g-PAA hydrogel loaded with INS has hypoglycemic effects. With different concentrations of CMC-g-PAA hydrogel co-cultured with Caco-2 cells, the cell survival rates are close to 100%, which indicates that the hydrogel has no cytotoxicity. In sum, the novel CMC-g-PAA hydrogel has a prospective application in the specific-site delivery of proteins and peptides.