Technical Abstract: Even though common spray drying has been widely used for drying food and related products, the effect of drying conditions of supercritical CO2 spray drying on the particle sizes of dried products has not been well studied. The objective of this study was to study the effect of drying conditions and design parameters on the particle sizes of biomaterials dried with supercritical CO2 spray drying. The ethyl cellulose (EC) microparticles were prepared with supercritical CO2 as the dry medium using an experimental spray drying apparatus. This research studied the influences of spray nozzle diameter, mass ratio of gas to liquid, solution concentration, temperature and pressure on the physical characteristics of ethyl cellulose microparticles. The results indicated that the average size of the dried particles ranged from 1.07 to 9.84 µm. The spray nozzle with 8 mm diameter produced smaller microparticles with narrower distribution than the 4mm spray nozzle. The average particle size increased with the increase of the ratio of gas to liquid. Also, the average size and distribution of the microparticles increased with the rise of temperature and solution concentration, but decreased with the increase of pressure.