Chitosan (CS) nanosphere loaded aspirin (aspirin/CS) was prepared by nucleation and ionic crosslinking in an emulsion used for medical and pharmaceutical applications. Chemical component, morphology, size distribution, and crystal structure of nanospheres were characterized by Fourier transform infrared (FTIR) spectroscopy, field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), dynamic laser light scattering (DLLS), and X-ray powder diffraction (XRD). Results showed that the diameter of a typical aspirin/CS nanosphere is about 88 nm and the distribution is uniform. The crystal structure of CS does not change during the nucleation process. The crystallinity of aspirin is dramatically reduced and aspirin is almost amorphous in the nanosphere. The drug content (mass fraction), the drug loading efficiency, and the in vitro release profiles under different conditions were investigated using UV-Vis spectrophotometry. Results showed that the drug content was about 55%, the drug loading efficiency reached 42%, and the chitosan nanosphere displayed an excellent drug. controlled release behavior under the experimental conditions.