Optical clearing is a well-known phenomenon. It is based on the matching of refractive indices of a bulk material and scattering particles. The same principle is also used in scattering-based optical measurements of different constituents, such as glucose. By registering changes in scattering, it is possible to evaluate changes in the concentration of a solvent. This work describes the use of optical coherence tomography (OCT) to monitor glucose-induced changes in the optical properties of samples. , mouse skin tissue, and mice (C57BL) are used as samples. Differences between in vitro and in vivo measurement conditions, the effect of glucose on the samples’ optical properties, as well as possible problems in OCT experiments are discussed. A comparison of OCT signals from mouse skin samples and mice in vivo shows that the intensity of backscattered radiation is stronger in a living animal than in cultured tissue. Moreover, the effect of glucose on the scattering properties is larger in an in vivo case than in an in vitro case. In comparison with tissue, the effect of glucose is the smallest in Intralipid. The results increase the value of using cultured tissue in developing optical sensing techniques.