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Forsythoside A (FTA) is the major bioactive component of the extracts from the Forsythiae fructus. The aim of the study is to investigate the absorption mechanism of FTA using Caco-2 cells in vitro and in situ intestinal perfusion model, and to illustrate why the bioavailability orally of FTA was low from the perspectives of absorption. From in situ intestinal perfusion model, the absorption of three different concentrations (2.6、 5.2、 10.4μg·mL-1) of FTA in different intestinal segments was studied with phenol red as the marker. It was shown that the effective permeability coefficient (Peff) of FTA with different concentrations had little significant difference from that obtained after perfusing via duodenum, jejunum and ileum. The Peff of FTA increased obviously after perfusing via duodenum, jejunum and ileum when EDTA(10μg·mL-1), Ciclosporin (10μg·mL-1), Probenecid (200μmol·L-1) and Verapamil (100μg·mL-1), respectively were added to the perfusion fluid, which showed dose-dependence, but Diclophenac Sodium (50μg·mL-1) was opposite.Besides, there was no significant change in the absorption of FTA when Mannitol of different concentrations was added to the perfusion fluid. As shown from in vitro Caco-2 cell model, the apparent permeability coefficients (Papp) of FTA were measured as a function of directions and concentrations. It was demonstrated that the mean of Papp was 4.089× 10-7cm/s in the apical to basolateral (AP-BL) and the efflux ratio was 1.00 approximately over the range of 2.6-10.4μg·mL-1 of FTA from bi-directional transport studies. The transport rate of FTA was dependent on the concentrations. Papp of FTA was not affected by transport directions, different FTA concentrations and SGLT1 inhibitor of different concentrations.In addition, Papp of FTA showed a tendency of increase with the EDTA, Ciclosporin, Probenecid and Verapamil concentrations increasing, but Diclophenac Sodium was opposite. The results above indicated that the absorption of FTA may be passive diffusion and had no difference in different segments of rat intestine. Besides, it was involved paracellular route transport. P-gp, MRPs and OATP may participate in the absorption of FTA in the intestine meanwhile. This observation may demonstrate the possibility that the low permeability of FTA contributes to its low bioavailability orally.