Low water solubility can lead to poor bioavailability of many hydrophobic pharmaceuticals in a biological system. One way to solve this problem is to reduce their particle sizes to nanometer scales so that the compounds can be dissolved in water by dispersion. Our group has successfully increased the water solubility and bioavailability of water insoluble compounds, soy isoflavones, using supercritical CO as an antisolvent to precipitate out isoflavones in the form of nanoparticles. Isoflavones are known as phytoestrogens since their chemical structures are similar to that of the female hormone, estrogen. Isoflavones can thus be used as a replacement for estrogen to treat women with menopausal symptoms, since prolonged intake of synthetic estrogen can increase the risk of developing breast cancer. Soy isoflavones can exist in nature in twelve different kinds of chemical entities; and genistein has the strongest estrogenic activity. In this study, we evaluated the impact of various process parameters of supercritical CO-based antisolvent precipitation method on particle formation. Among the three parameters tested in this study-pressure of precipitation, concentration of drug solution, and feed rate ratio of CO/drug solution, we found that the pressure is the most important parameter which can greatly affect the particle size. Using the optimized experimental conditions of supercritical CO, the size of genistein particle has been successfully reduced from its original size of more than 50 μm to around 220 nm as determined by scanning electron microscopy. Finally, the 24-hour pharmacokinetic study performed in rats showed that the plasma concentration of genistein has increased by 75% after nanomization demonstrating the possibility of improving the bioavailability of water insoluble compounds using the supercritical antisolvent (SAS) process. The generic technique developed in this study can be used to generate more efficacious pharmaceuticals and health care products, including water-insoluble compounds isolated from Chinese herbal medicines.