Our previous research showed that a simple ultra-high-pressure process made poly(vinyl alcohol) (PVA) solution into a macrogel and nanoparticles. To investigate the release properties of PVA hydrogels prepared by the ultra-high-pressure treatment, we prepared hydrogels containing model drugs by pressurizing a PVA solution with Alfa-G Hesperidin or Oil Blue N as a water-soluble or an oil-soluble model drug, respectively. In the case of the oil-soluble drug, an oil-in-water emulsion, Oil Blue N containing dodecane in a PVA solution, was used by homogenization before pressurization. The average diameter and the diameter distribution of oil droplets before and after the ultra-high-pressure treatment were almost the same. However, the PVA hydrogel prepared at 10,000 atm for 10 min exhibited the slowest release rate of model drugs. Thus, we found that the release rates of the model drugs from the PVA hydrogels were controlled by the degree of crosslinking in the resulting gels, which was determined from the operation parameters of the ultrahigh-pressure treatment, such as the pressure, time, and concentration of the PVA solution. Therefore, an ultrahigh-pressure process is promising for drug-carrier development because of the nonharmful simple preparation process. (C) 2010 Wiley Periodicals, Inc. J Appl Polym Sci 119: 2725-2729, 2011