Objective This study aimed to observe the functional application of shock wave（SW）in transdermal drug delivery （TDD）and to explore the distribution of drugs after transdermal administration by two types of shock wave. Methods Nine female Sprague-Dawley（SD）rats were randomly divided into 3 groups: ①control group; ② RESW group（0.35 mJ/mm2，2 Hz，400 pulse）;③ FESW group（0.16 mJ/mm2，2 Hz，400 pulse）. Micro positron emission tomography/computed tomography（MPET/CT）was used to observe the distribution of [18]F-NaF. Furthermore，12 SD rats were randomly divided into 4 groups: ① control group; ② FESW group 1 （0.03 mJ/mm2，2 Hz，400 pulse）; ③FESW group 2（0.16 mJ/mm2，2 Hz，400 pulse）; ④ FESW group 3（0.35 mJ/mm2，2 Hz，400 pulse）. High-performance liquid chromatography（HPLC）was used to test the penetration efficiency of diclofenac sodium and glucose treated with FESW. Statistical significance was conducted by analysis of variance of repeated measurement. Results It was observed by MPET/CT that FESW could penetrate [18]F-NaF through the skin，while RESW could not. The second stage study found that within a certain energy range，the higher the energy of FESW，the stronger its permeability. 5 hours later，compared with the control group，the drug concentration of diclofenac sodium group（control group 160.947 ± 14.973; FESW 1 group 189.833 ± 19.202; FESW group 2 298.464 ± 61.304; FESW group 3 267.088 ± 32.783）and glucose group（control group 17.790 ± 2.944; FESW 1 group 58.959 ± 17.409; FESW group 2 54.279 ± 7.76; FESW group 3 56.417 ± 3.397）under different energy was measured. Repeated measures analysis of variance showed that the within-subject effect（diclofenac sodium，F=4.77，p=0.03; glucose，F = 8.95，P = 0.006）was significantly different among the control group，FESW group 1 and FESW group 2（P < 0.05）. Conclusion The study found that FESW had good drug permeability and could penetrate [18]F-NaF，glucose and diclofenac sodium into the rat body，which provided new biological evidence for new route administration.