The supercritical fluid expansion depressurization (SFED) process is a novel technique proposed recently to prepare microparticles with narrow size distribution. The process has shown a very promising potential in pharmaceutical micronization. An SFED experimental apparatus was set up and griseofulvin (GF) microparticles were prepared successfully with the solvent of the mixture of acetone and ethanol. The influences of the operation parameters, including the pressure and temperature in the mixing vessel, the solution concentration and the solution feeding rate, on the particle morphology, size and size distribution were investigated in detail. The results show that approximately spherical particles with size less than 1.5 mu m can be prepared successfully by SFED process. The pressure in the mixing vessel and the solution feeding rate are two most effective parameters while the solution concentration is the next, and the temperature in the mixing vessel has little effect on the GF particles. The optimal operation condition for preparing GF micro-particles in the range of this work is: the pressure of 8 MPa and the temperature of 60 degrees C in the mixing vessel, the solution feeding rate of 9 ml/min and the solution concentration of 15 mg/ml. (c) 2007 Elsevier B.V. All rights reserved.