Abstract: By using Amitriptyline Hydrochloride as the model drug，amitriptyline hydrochloride-chitosan microspheres were prepared by emulsion cross-linking techniques with ethylene glycol diglycidyl ether （EGDE) as a cross-linking agent. The physicochemical properties and the drug-release performances of the microspheres were investigated. EGDE has epoxy groups and cross-linking reaction occurred with the groups of -NH2 on CS. The microspheres have the color of white, a spherical shape and an average diameter about 12.32m. The drug loaded efficiency is 26.25% and the content of the drug is 6.56%(/). With the increase of the concentration of CS , the releasing ratio of Amitriptyline Hydrochloride decreases. The result indicated that the microspheres have a satisfactory performance of slowly releasing the drug of Amitriptyline Hydrochloride.