A modified supercritical antisolvent technique (solution enhanced dispersion with enhanced mass transfer using ultrasound in supercritical CO2, SEDS-EM) has been applied in preparation of PEG loaded PLA nanoparticles. The hydrophilicity of polylactic acid (PLA) nanoparticles has been increased by adding polyethylene glycol (PEG) in order to improve PLA as a controlled release drug system. Uniform distribution of solution tiny droplets by the SEDS-EM method in supercritical CO2 prevents particle agglomeration as well as intensifies the effect of mass transfer. The effects of PEG amount in the PLA/PEG polymer mixture and ultrasonic system on the formation of PLA-PEG nanoparticles have been studied. Operational parameters, such as temperature, pressure, ultrasound power supply and solution flow rate have been also investigated in the current paper. The morphology of PLA-PEG nanoparticles changed from hollow combined structure to nearly spherical form by decreasing the amount of PEG in the PLA/PEG polymer mixture. In addition, particle size reduction has been achieved by decreasing temperature, solution flow rate as well as by increasing pressure and providing ultrasound treatment. (C) 2012 Elsevier B.V. All rights reserved.