Laser-based photo-thermal therapies can provide minimally-invasive treatment of cancers. Their effectiveness is limited by light penetration depth in tissue due to its highly scattering properties. The highly disordered refractive index distribution in tissue leads to multiple-scattering of incident light. It has been hypothesized that mechanical compression has a great potential to enhance the capabilities of laser therapy by inducing localized water transport, decreasing the refractive index mismatch, and decreasing the scattering coefficient of tissue. To better understand this process, we investigated the refractive index change of ex-vivo dog skin during mechanical compression using a swept-source optical coherence tomography (OCT) device built in our lab. The Lorentz-Lorenz rule of mixtures was applied to evaluate the water and protein weight fraction of tissue simultaneously. Results show that the refractive index of skin increased from 1.38 to 1.52 during compression and water content decreased about 60%-70% when the skin sample was compressed by 70%. In addition, we conducted compression experiments on human finger, palm, back of hand, and front of forearm in vivo. OCT images of these skin sites before and after compression by 1 minute were compared. Optical thickness of epidermis and light penetration depth in the dermis were measured. The extended Huygens-Fresnel model was applied to measure the scattering coefficient μs of skin specimens. μs of skin was measured to be about 10-17 mm-1 before compression and decreased 60%-80% after compression, which increases the averaged light intensity by 2-7 dB and almost doubles light penetration depth in dermis. It is quite significant in laser therapies especially for treating epithelia cancers which originate at 1-2 mm beneath the tissue surface. In the OCT imaging of skin dehydration experiment, we conclude that dehydration is an important mechanism of mechanical clearing. / Master of Science