Purpose: The purpose of this research is to study the effects of three kinds of polyamines on the intestinal absorption of FDs across the rat intestine, assess their intestinal toxicity and elucidate their intestinal absorption enhancing mechanism.Methods: The absorption of FDs across the rat intestinal membranes and intestinal membrane toxicity were examined by an in-situ closed loop method.The transepithelial electrical resistance (TEER) was measured using a short-circuit current amplifier and membrane fluidity was examined by determining the fluorescence polarization of brush border membrane vesicles labled by DPH and TMA-DPH in the presence and absence of various polyamines.Results: Spermine and spermidine could improve the intestinal absorption of FDs and the enhancing effects of these polyamines were greater in the jejunum than in the colon.Of these polyamines,spermine had the greatest enhancing effect both in jejunum and in colon and did not cause any intestinal damage and morphological change.Furthermore, spermine and other polyamines had no effect on the membrane fluidity of brush border membrane vesicles labeled by DPH and/or TMA-DPH.On the other hand, spermine could moderately decrease the TEER value compared with the control.These results indicated that spermine may loosen the tight junction of the intestinal epithelium,thereby improving the intestinal absorption of drugs.Conclusion: Spermine and spermidine could improve the intestinal absorption of FDs in rats and did not cause any significant membrane toxicity, indicating that they would be promising and safe absorption enhancers for improving the intestinal absorption of poorly absorbable drugs.