Ibuprofen is an effective non-steroidal anti-inflammatory drug (NSAID), but it has several limitations in clinical application because of low solubility in water and gastrointestinal irritation. A water-soluble salt of ibuprofen, ibuprofen lysinate, has been synthesized to overcome these shortcomings, and it was formulated as suppository for rectal administration. Witepsol and polyethylene glycols were employed as suppository bases for either ibuprofen or ibuprofen lysinate, in order to compare the bioavailability in rabbits. The plasma concentrations of ibuprofen were assayed by HPLC after a rectal administration of ibuprofen and ibuprofen lysinate, respectively. In addition to the comparison of two suppository bases, the other factors which affect on rectal absorption were also evaluated, especially in the point of not only particle size and shape of ibuprofen lysinate but also effects of additives such as stearic acid, cetyl alcohol and capric acid. And pharmacokinetic parameters such as AUC, C_(max), and t_(max) were also compared. In conclusion, spray-dried ibuprofen lysinate which was polyporous and spherical shape gave an increased absorption from the rectal formulations with Witepsol H15 and stearic acid.