The study of the bioeffects of ultrasound and their etiology is of fundamental importance as a part of basic biophysics. In general, the most fruitful approach to the study of bioeffects of physical agents is the mechanistic one. The ultrasonic mechanisms include the mechanical effect, convective effect, cavitation effect, and thermal effect. In this research, the test skin was radiated the ultrasound using the medical equipment and analyzed the permeation of skin. However, it is not sufficiently to analyze the quantitative of the sonophoresis by the medical equipment setup. To solve the above-mentioned problem, the oscillation of the stratum corneum in response to the ultrasound radiation is simulated using Rayleigh-Plesset¡¦s bubble activation theory. To calculate the resonance frequency domain of bubbles attached of pig skin which is around 15 to 36 kHz that called low frequency and it caused gas body activation on test skin. We choose 20 kHz in the resonance frequency domain to compared with 10, 60 kHz as non-resonance frequency. 1.9 and 13.6 mW/cm2 of the sound intensity which are respectively lower and higher than cavitation threshold intensity are used. The result of low frequency sonophoresis presented that high permeation rate is caused by resonance frequency 20 kHz. And according to the experiment, it is also proved that the experiment of low frequency sonophoresis only took 1/160 of the sound intensity and 1/4 of the time for the high frequency sonophoresis. Furthermore, the research examined the uniformity of the sound field, and a wedge is designed to make a diffused field to compare the effect between a uniform one and its contrast. The result presented that the permeating drug with uninformative field is twice the amount of the normal exposure ultrasound field. Based on the above results, the changes of frequency, sound intensity and sound field uniformity, the enhancement effects of the sonophoresis will be achieved.