In order to avoid the irritation of metformin hydrochloride to the stomach and realize its release in the intestine, with metformin hydrochloride as the main drug and chitosan/sodium alginate as the composite support, the optimal formulation and preparation technology of metformin hydrochloride loaded pH-sensitive hydrogel microspheres were selected, and the pH-sensitivity and in vitro drug release characteristics were investigated. The formulation and process were optimized by single factor test and orthogonal test. The morphology was characterized by SEM. The entrapment efficiency and drug-loaded amount were determined by UV. The release degree was studied by rotating basket method. The results show that the optimized prescription is as following: chitosan and sodium alginate with a total concentration of 2%(mass-volume ratio), mass ratio of sodium alginate to chitosan =1∶1, mass ratio of drug to sodium alginate=2∶5, and 3.5% CaCl2(mass-volume ratio). The cumulative release rate is less than 4% in artificial gastric juice within 6 h, and up to 96.4% in artificial intestinal juice within 6 h. The formulation and process are stable and reliable, and the hydrogel microspheres have high mechanical strength, good biodegradability and stability. So it is a new metformin hydrochloride delivery system.