Aiming at improving controlling precision of drug permeation in low frequency sonophoresis (LFS), an ultrasonic transducer with sealed structure is designed to change the pressure of drug liquid in LFS, based on finite element calculation and analysis. The influence of sealed system on transdermal process can be investigated by vitro experiments on skins (including artificial skins and rat skins) permeation through a Franz diffusion cell system. The results demonstrate that ultrasonic cavitations, penetration enhancers and the pressure can change the permeability of skin. Ultrasound can damage the surface structure on the skin to increase the permeation due to the ultrasonic cavitations, and the pressure, ultrasound and penetration enhancers can be used to improve the accuracy of drug penetration effect together. Therefore, this ultrasonic transducer with a sealed structure can preliminarily realize pressure change in LFS to adjust the precision of transdermal drug delivery, which can be beneficial for the further design of ultrasonic transducer with controlled pressure in LFS applications.