Herbal products can interfere with allopathic medicinal treatment through pharmacokinetic and pharmacodynamic interactions. Pharmacokinetic interactions that alter drug absorption may cause variable and/or unsatisfactory drug bioavailability, however, an absorption enhancing effect may be used under controlled conditions to ensure sufficient drug absorption of poorly absorbable drugs. The effect of the hydrochloride salt of sinomenine, an alkaloid obtained from the plant Sinomenium acutum, on the transepithelial electrical resistance and transport of different compounds (including cimetidine, vitamine C, rutin, luteolin and insulin) across Caco-2 epithelial cell monolayers was investigated in this study. Sinomenine HCl induced a concentration dependent decrease in the transepithelial electrical resistance values of the Caco-2 cell monolayers, which was completely reversible. Sinomenine HCl also significantly increased the transport of all the test compounds in the apical-to-basolateral direction compared to the control group and decreased the basolateral-to-apical direction of a P-glycoprotein substrate, cimetidine. From these results it can be concluded that sinomenine HCl increases drug absorption across the intestinal epithelium by means of one or more mechanisms including a transient opening of the tight junctions (as indicated by a reduction in transepithelial electrical resistance) to allow for paracellular transport and/or inhibition of active drug efflux (as indicated by inhibition of basolateral-to-apical transport of cimetidine).