With a novel antidiabetic nateglinide as the model drug, nateglinide- chitosan microspheres were prepared by emulsion cross-linking techniques with glutaric dialehyde(GD) as cross-linking agent, chitosan(CS) as polymeric carrier, and nateglinide as the model drug. The influence of various conditions on microspheres' physicochemical properties and the drug-release performances were investigated. The results indicated that the microspheres had a spherical shape with a average diameter of 2.054m, and were tan in color. The drug content was 9.12%(mass fraction) and the drug encapsulation efficiency reached 48.9%. XRD analysis indicates that nateglinide in microspheres is mainly amorphous. The results of drug release in vitro show that the microspheres have a satisfactory performance of slowly and steady releasing the nateglinide. With increase of the concentration of chitosan, the release rate of nateglinide decreased, and the release rate of nateglinide in the acidic buffer is faster than in the weak alkaline buffer.