Abstract The effects of 1- O-ethyl-3-butylcyclohexanol (OEBC) on the in vitro skin permeation of ten model drugs with different physicochemical properties across excised rat skin were evaluated. The results showed that the addition of OEBC significantly improved the in vitro skin permeation of the model drugs compared with the control (without OEBC). To clarify the promoting mechanism of OEBC, a multiple regression analysis was employed. When the permeation study was performed without OEBC, the permeability coefficient was quantitatively predicted as a linear function of molecular weight (log MW) and their lipophilicity (partition coefficient of drugs between octanol and water (log K o/w)) with a sufficiently high correlation coefficient ( r=0.842). It was suggested that skin permeation of drugs without OEBC was explained as a function of diffusion of drugs through the skin and partitioning of drugs to the skin. Although OEBC was administered, the permeability coefficient of drugs cannot be predicted as a linear function of log MW and log K o/w ( r=0.572).