The aim of this study was to investigate if the effective in-situ permeability (Peff) of a new growth hormone-releasing peptide, hexarelin, along rat intestine was enhanced by a lipid matrix drug-delivery system comprising a mixture of soybean phosphatidyl choline and medium-chain monoacylglycerol (PC-MG). The study was performed with and without a protease inhibitor, Pefabloc SC. To enable better understanding of the mechanism of action of this delivery system we also studied the uptake of a small hydrophilic molecule, atenolol. PC-MG at a concentration of 15 mmol L(-1) increased the jejunal Peff of hexarelin approximately 20-fold, both in the presence and absence of Pefabloc SC, whereas Peff was not increased in the ileum and colon. PC-MG had no effect on the jejunal, ileal and colonic Peff of atenolol. Complete recovery of the non-absorbable molecule PEG 4000 showed that functional intestinal viability was maintained in all experiments. Although the results obtained in this study are promising, pharmacokinetic and toxicological studies are required to investigate if this delivery system is a suitable and safe candidate for improving the oral bioavailability of hexarelin.