In this report, we have determined the uptake of salicylic acid (SA) by liposomes and proposed the pH-dependent but not carrier-mediated transport mechanisms of SA through the lipid bilayer. The permeability of various drugs to the liposomal membrane, estimated from their inhibitory effects on SA uptake, correlated well with their permeability to rat intestinal membrane in vivo, and that to Caco-2 monolayer in vitro. In addition, the high permeability of SA or benzoic acid to the lipid bilayer was confirmed by means of molecular mechanics calculations in which the polar surface area and the electrical potential of drug molecules were used as the parameters of their permeability. Our results could be expected to describe the mechanisms of the intestinal absorption of monocarboxylic acid drugs.