The purpose of this study was to determine the effects of iontophoresis on transdermal delivery of procaine hydrochloride in healthy volunteers, as well as to the synergic effect of high voltage current or ultrasound on the efficacy of transdermal delivery of iontophoresis. Forty healthy volunteers were randomly assigned to four groups topical application group (TA), iontophoresis group (IT), pre-treatment of high voltage current stimulation with iontophoresis (HVS + IT), and pre-treatment of ultrasound application with iontophoresis (US + IT). All subjects received procaine iontophoresis on the forearm using direct current with 4 mA f3r 15 minutes. All subject was measured the duration of local anesthesia, pressure pain threshold, pain perception threshold using rectangular wave at 0.2 ms, 1 ms, 50 ms of rectangular current stimulation after procaine iontophoresis. For comparisons of the sensory characteristics and efficacy of iontophoresis between the groups, an one-way ANOVA and Kruskal-Wallis were used. The significant difference the duration of local anesthesia were found between the groups (p<0.001). The local anesthetic duration of IT, HVS+IT were significantly longer than TA. Meanwhile, the local anesthetic duration of US+IT was significantly longer than HVS+IT, IT and TA group (p<0.05). Also, the pressure pain threshold, pain perception threshold at 0.2 ms, 1 ms, 50 ms were significant difference between the groups (p<0.001). All sensory characteristics including pressure pain threshold, pain perception threshold of IT, HVS+IT was significantly increased than TA, whereas, US+1T was significantly increased HVS+1T, IT and TA (p<0.05). This study showed that the procaine iontophoresis have increase the duration of local anesthesia concomitantly pressure pain threshold and pain perception threshold of sensory nerve fibers such as $A-{eta}$, $A-{delta}$ and C fiber. This findings suggest that the iontophoresis enhanced the transdermal delivery of drug ions in vivo. The combination of ultrasound application and iontophoresis synergized the transdermal delivery of drug ions. It is suggests that an electric field, mechanical and heating property of ultrasound may contribute to synergic effect due to temporary changes of structure in the stratum corneum.