Rapid expansion of supercritical solution (RESS) is the most common method of pharmaceutical particle forming approaches using supercritical fluids. The RESS method is a technology which produces a small solid product with a very narrow particle size distribution, organic solvent-free particles. This process is also simple and easy to control the operating parameters in comparison with other methods based on supercritical techniques. In this study, Ibuprofen, anon steroidal anti-inflammatory drugs (NSAID), has been micronized by RESS; the size and morphology effects of three different RESS parameters including extraction temperatures, extraction pressures and expansion nozzle temperatures have been investigated and optimized by response surface method. The particle size distribution has been measured by Light diffraction scattering (LDS) method. SEM has been used to analyze the surface structure, DSC and FTIR for thermal and chemical structure analysis. The obtained results are average particle sizes below 1 µm decreased significantly compared to the initial particle size and the optimal operating conditions are identified, enabled the pilot-scale studies and industrial operation.