To enlarge the application of spray drying technology on the preparation of biomaterial microparticles, the ethyl cellulose microparticles were prepared by using the supercritical CO₂ as the drying medium on the experimental apparatus designed by the authors. The effects of spray nozzle diameters, mass ratio of gas to liquid, solution concentration, temperature, and pressure on the physical characteristics of ethyl cellulose microparticles were studied. The results showed that the mean size of the microparticles ranging between 1.07 and 9.84 μm could be obtained. The average size of microparticles prepared by the spray nozzle which diameter was 8 mm was smaller than that by the spray nozzle which diameter was 4 mm, and the particle size distribution of microparticle prepared by the former spray nozzle was narrower than that by the latter. With the increasing of mass ratio of gas to liquid, the microparticles that the average size was the biggest could be obtained. The average size of microparticles increase and the particle size distributions enlargement with the increasing of temperature and solution concentration were found, and the results that the average size of microparticles decreases and the particle size distributions reduce with increasing of pressure were also observed.