We investigated sorption and permeation of emedastine with 11 different vehicles, composed of single or binary solvents, in excised rat skin. In the sorption study, partition parameters of the drug with each vehicle were obtained by dividing the drug amount in skin at equilibrium by its donor concentration. When the logarithm of the partition parameters for the stratum corneum/vehicle partitioning (Ks') was plotted against the dielectric constants of the vehicles, a bi-linear relationship was obtained. The skin flux of emedastine largely differ among the vehicles. A quasi-steady-state flux of emedastine exhibited a good linear relationship with Ks', except for ethanol (EtOH)/isopropyl myristate (IPM) systems, indicating that the partitioning process is critical in determining the permeation rate. Delineation of the EtOH/IPM systems would be due to an increase in the diffusivity of the drug in the stratum corneum, as indicated by the analysis using a two-layer diffusion model. Thus, differential evaluation of partitioning and diffusion processes by both sorption and permeation studies would give further insights into the effects of vehicles on skin permeation of drugs.