Nowadays one of the worries in field of medicine is decreasing damages from drug consumption, which occurs because of non-selectivity of medications and absorption of them by irrelevant organs. Researchers attempt to find appropriate ways by using drug delivery systems to decrease drug consumption risks. One of most important ways is drug delivery with micro or nanoparticles that coated with drugs. This particles don’t stimulate immune system and they can absorbed by target organ or cellular. Because of these advantages of micro and nanoparticles, in this research chitosan bio-polymer which used as a pharmaceutical base, successfully brought to nanoscale by the use of Rapid Expansion of Supercritical (RESS) apparatus with carbon dioxide as a solvent and acetone as a co-solvent. Also the effects of parameters such as pressure (in range of 70 – 220 bar), temperature (I range of 30 – 70 degrees of centigrade) and nozzle diameter (between 500 – 1200 micro meters) observed as follow: Increase of pressure caused decrease in average particle size of products although increase of nozzle diameter led particles to increase in size and finally as the temperature increased at first made products smaller but after 64 degrees of centigrade increase of temperature made them larger and larger. The best products of this research related to temperature of 64°C, pressure of 198 bar and 500 micro meter nozzle diameter which produced 81 nanometer average particle size.
