Abstract: This study was to prepare ketoprofen loaded microemulsion-based hydrogel(MBH) and investigate its transdermal mechanism.The pseudo-ternary phase diagrams for O/W microemulsion regions were constructed.Various microemulsion formulations were prepared and the abilities of various microemulsions to deliver ketoprofen through the skin were evaluated in vitro using Franz diffusion cells fitted with mouse skins.The data showed that the drug in microemulsions/MBH resorted in skin (705.13±33.18) and (502.75±28.54) μg/cm²,which were 4.66 and 3.22 times the control group.The DSC and HE studies showed that microemulsion/MBH affected the normal lipid packing of stratum corneum to enhance the drug permeation.Coumarin-6 labeled preparation were mainly distributed in the stratum corneum and hair follicle.