Purpose: This study conducted the following experiment to examine transdermal permeation effects or 500 KHz ultrasound with lidocaine HCl. Methods; First, to experiment skin permeation enhancement effects of 500 KHz ultrasound frequency, it produced apparatus and transducer of 500 KHz ultrasound and Franz diffusion cell for skim permenation experiment suitable to purposes of the experiment. Transdermal permeation experiment applied Lidocaine HCL gel to skin of hairless mouse depending on ultrasound frequency and duty cycle and analyzed permeation ratio with HPLC. Results: As a result of fixing lidocaine HCl gel at the same intensity with pulsed mode and continuous mode and comparing transdermal permeation ratio by frequency, transdermal permeation ratio was increased at 500 KHz ultrasound and remarkably increased at continuous ultrasound. It was found that 1 MHz and 500 KHz ultrasound in transdermal permeation experiment enhanced transdermal permeation of lidocaine HCl. In particular, transdermal permeation of 500 KHz using lidocaine HCl gel was highest. Conclusion: However, researches considering various frequencies, intensities and application hours in low frequency areas including 500 KHz ultrasound are needed to increase deep permeation or drugs.