Systems and methods for photobiomodulation of biological processes using invasive or non-invasive chemical clarification of biological tissues are provided to improve optical transmission of light energy in sub-epidermal tissue. The chemical clarification of in vivo biological tissues provides at least partial optical clarification of such tissues by applying a clarifying agent to the sub-epidermal tissue to temporarily replace water and other fluids from such tissues. Light energy is then applied to the clarified tissues, providing for deeper penetration of the light energy and more effective photobiomodulation. Lower power and wavelengths of light can be administered at high fluences into the tissue, at greater depths, and induce biological effects that are more pronounced than previously observed.