Abstract: AimTo study the enhancement effect and mechanism of sodium N-［8-(2-hydroxybenzyl)amino］ caprylate (SNAC - a kind of synthetic enhancer) to insulin (INS) solution in gastrointestine. Methods To determine the enhancement effect of SNAC on INS absorption by oral administration to rats and mice; To study the enhancement mechanism of SNAC by three kinds of methods: delivering SNAC and INS solution to different parts of rats' intestines, adding energy inhibitor 2,4-dinitrophenol (DNP) or P-glycoprotein (P-gp) inhibitor verapamil (Ver) into SNAC and INS solution. ResultsSNAC was shown to enhance the gastrointestinal absorption of INS, the intensity of absorption enhancement corresponded to the doses of SNAC. The enhancement of SNAC to INS in different parts of the rat intestine was different (jejunum > colon > ileum). The effect of SNAC on INS absorption increased accordingly. ConclusionThe enhancement of SNAC to INS absorption presented dose dependence on SNAC; the absorption process needed energy and related to P-gp efflux.