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Objective:To investigate the percutaneous penetration effect of essential oil of mint fromMentha haplocalyx Briq.on the complex active components in Chinese herbal extal preparations,and assess its toxicity on the skin cells.Methods:The cytotoxicity of mint oil on HaCaT keratinocytes and CCC-ESF-1 fibroblasts was measured using an MTT assay.Five model drugs with a wide range of lipophilicity,namely osthole,tetramethylpyrazine,ferulic acid,puerarin,and geniposide,were tested using in vitro permeation studies to investigate the percutaneous penetration enhancement effect of mint oil.Secondary structure alterations of skin stratum ceum (SC) were measured using Fourier transform infrared spectroscopy (FTIR).Saturation solubilities and SC/vehicle partition coefficients of the five model drugs with and without mint oil were also determined to understand the potential mechanisms of the essential oil.Results:Half maximal inhibitory concentration (IC50) values of mint oil were significantly higher in HaCaT and CCC-ESF-1 cell lines than values in the well-established and standard penetration enhancer Azone.Conclusions:Mint oil at proper concentration could effectively facilitate percutaneous penetration of both lipophilic and hydrophilic drugs,and exhibit higher efficiency for moderate hydrophilic drugs.Mechanisms of penetration enhancement by mint oil could be explained with saturation solubility,SC/vehicle partition coefficient and the secondary structure change of SC.