© 2019 World Federation for Ultrasound in Medicine & Biology Exposure of the skin to low-frequency ultrasound in the Franz diffusion cell has been found to increase the permeability of the skin to molecular transport. In many cases, significant heating of the coupling fluid requires the use of duty cycles that extend the total experimental time. This is a methodological study in which the coupling fluid is circulated between a modified Franz diffusion cell and a heat exchanger to allow for the continuous application of low-frequency ultrasound while the coupling fluid temperature is held constant. Dermatomed porcine skin was exposed to continuous ultrasound at 20 kHz for 10 min at an intensity of 55 W/cm2 while the coupling fluid was maintained at one of three target temperatures (13°C, 33°C or 46°C). Foil pitting and passive cavitation detection revealed that inertial cavitation activity decreased with increasing coupling fluid target temperature. Transport measurements revealed an increase in mean donor calcein concentration with increasing coupling fluid temperature, though these were not statistically significant. Taken together these findings suggest that the weakened stratum corneum lipid structure at higher temperatures is more susceptible to the introduction of defects from the jetting of cavitation.