The RESS method was used to manufacture the fine particles of diclofenac. A reduction in particle size increases the dissolution rate of the drugs in the biological fluids and enhances the bioavailability of them in body. CO2 was used as the supercritical fluid because of its mild critical temperature (31.1 degrees C) and pressure (7.38 MPa). In this study, effect of extraction temperature (313-333 K), extraction pressure (14-220 MPa), spraying distance (1-10 cm), nozzle length (2-15 mm) and effective nozzle diameter (450-1700 mu m) were investigated. Based on the different experimental conditions, the average particle size of diclofenac was between 10.92 and 1.33 mu m. The size and morphology of the micronized diclofenac particles were monitored by scanning electron microscopy (SEM). The SEM images show a successful size reduction of virgin diclofenac particles. In all the experiments, the parameters had moderate effect on the mean particle size of the diclofenac. Also, the morphology of the processed particles was change to quasi-spherical and irregular while the virgin particles of diclofenac were irregular in shape. (C) 2010 The Society of Powder Technology Japan. Published by Elsevier B.V. and The Society of Powder Technology Japan. All rights reserved.