This study investigated the pressurized carbon dioxide anti-solvent co-precipitation process (abbr. PAS) on encapsulation of propolis with water soluble polyethylene glycol (PEG). The extent to which recovery of propolis flavonoids, total yield, amount of propolis (i.e. drug content) affects the precipitation was examined using a two-factor central composite schemed experimental design method. Analysis results indicated that the drug content and total yield of the precipitates are conversely related to each other in the PAS process. Additionally, micro-sized amorphous particulates of propolis encapsulated on the surface of PEG were generated, as evidenced by chromatography and X-ray diffraction analyses. Total yield of the PAS co-precipitation process reached 88%, and recovery of propolis flavonoids achieved 97%. Experimental results also indicated that the concentration ratio of propolis to PEG in the feed more significantly affects the drug content than that of the pressure factor. Moreover, nearly spherical and aggregated micro-sized co-precipitated particulates are more soluble in an aqueous solution than those of ethanol extracts. (C) 2014 Elsevier B.V. All rights reserved.