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The purpose of this study was to compare intestinal permeability between enantiomers of 2-(2-hydroxypropanamido) benzoic acid (( R) -/( S) -HPABA), a marine-derived antiinflammatory drug, using an in situ single-pass intestinal perfusion (SPIP) model in rats. Concentrations, isolated regions of small intestine, and p-glycoprotein (P-gp) inhibitor were performed to investigate their influences on the intestinal absorption of ( R) -/( S) -HPABA. In addition, a molecular docking method was performed to illustrate our prediction. The absorption rate coefficients ( K a) and permeability values ( P eff) of ( R) -/( S) -HPABA were calculated. The permeability of ( S)-HPABA was significantly ( P < 0.01) higher than that of ( R)-HPABA in jejunum, and ileum permeability of ( R) -/( S) -HPABA appeared best in ileum; the investigated concentrations ranged from 20 to 80 μg/mL, K a and P eff values of ( R) -/( S) -HPABA increased linearly; in the presence of P-gp inhibitor (verapamil), P eff values of two enantiomers were increased significantly; and the effect of P-gp on absorption of ( R)-HPABA is stronger than that of ( S)-HPABA in ileum segment. Based on these results, carrier-mediated transport or passive transport combined with carrier-mediated transport seems to be the mechanism for intestinal absorption of ( R) -/( S) -HPABA, and ( R) -/( S) -HPABA may be recognized as the P-gp substrate. In addition, the intestinal permeability of ( S)-HPABA is higher than that of ( R)-HPABA. [ABSTRACT FROM AUTHOR]