Abstract: Chitosan hydrogel (CS–Ma–Gel) was constructed by ionic crosslinking of maleic acid. Taking Amoxicillin (Am) as the model drug, the drug loaded hydrogel (Am/CS-Ma-Gel) was prepared. The structure and morphology of the hydrogels were characterized by FT-IR, UV-Vis, SEM and so on. The swelling property and drug sustained release behavior for the hydrogels were investigated in different pH media. The experiment results indicated that Am was uniformly dispersed in CS–Ma–Gel hydrogel network without phase separation. Both the swelling property and Am sustained release behavior for the hydrogels exhibited pH responsiveness. In pH 2.00, 4.00, 6.86 and 9.18 media, the swelling rates of CS-Ma-Gel were 800%, 2200%, 760% and 1300%, respectively. Cumulative drug release rates of Am/CS-Ma-Gel were 24.6%, 70.4%, 35.7% and 50.4% for 42 h, respectively. The swelling rate and drug cumulative release rate in acidic and alkaline media were higher than those in neutral media, and the drug release capacity was positively correlated with the swelling property. The preparation method of Am/CS–Ma–Gel is simple and green. Am/CS–Ma–Gel shows the characteristics of amphoteric ionic pH-responsive hydrogel. The research lays a theory and experiment foundation for the development of chitosan sustained release materials.