Ibuprofen-eugenol ester (IEE), a highly lipophilic compound, was synthesized from ibuprofen in order to reduce the common side effects induced by this classic anti-inflammatory drug. IEE was isolated as an amorphous whitish solid with a melting point at 40.2 +/- 0.1 degrees C, whose structure was confirmed by IR, 1H NMR and MS spectra. The hydrolysis results showed that the ester was stable over a wide pH range from 1.1-9.96. However, it could be hydrolyzed easily by enzymes from rat plasma and rat liver homogenate. A pharmaceutically acceptable microemulsion system was presented and characterized in terms of stability, droplet size distribution (DSD) and their solubilization capacity for IEE. The solubility of IEE in the optimized microemulsion formulation was about 21,000 times higher than that in water. The AUC of ibuprofen from the prodrug showed a remarkable increase compared to oral ibuprofen suspension. These results suggest that synthesizing the ibuprofen prodrug was justified and the presented microemulsion system might be a promising oral dosage form for poorly water-soluble drugs.