A comparative study of physical, chemical, and combined enhancement of transdermal transport of optical clearing agents (OCAs) is presented. As a physical enhancer of diffusivity, ultrasound (US) with a frequency 1 MHz and a power 1.1 W in the continuous mode was used, and dimethyl sulfoxide (DMSO) was used as a chemical enhancer. OCA (glycerol and polyethylene glycol-400 in equal proportion) was topically applied to the rat skin in vivo as alone or as together with the enhancers. Monitoring of skin optical clearing was implemented using an optical coherence tomography. The results have shown that the attenuation coefficient of intact skin dermis after the application of US-DMSO-OCA, US-OCA (both for 4 min), and DMSO-OCA (for 20 min) combinations decreased approximately by 31%, 19%, and 5%, respectively, while OCA alone did not induce a noticeable clearing effect for 20 min. Control skin sites with removed epidermis were used for modeling the upper limit of dermis optical clearing, i.e., maximal degree of optical clearing, by using the studied enhancers. They demonstrated that the attenuation coefficient decreases by 32%, 30%, 17%, and 16% at the action of US-DMSO-OCA, US-OCA, DMSO-OCA, and OCA, respectively. It can be concluded that US-DMSO-OCA combination only allowed reaching the upper limit of skin optical clearing.