This work used Candida rugosa lipase to resolve racemic Naproxen by esterification with ethanol, n-butanol, n-hexanol, or n-decanol in supercritical CO2, It was found that the lipase enantioselectively, esterified (S)-Naproxen within all systems. The enantiomeric ratio increased four folds by slightly decreasing the alcohol concentration, The ef feet of the alcohol concentration on the enantioselectivity was greater than that of changing acyl accepters.