The potential of magnetic resonance imaging (MRI) pulse sequences for monitoring local changes in proton relaxation times after the local application of skin optical clearing (OC) compositions in vivo has so far remained largely unexplored. Mouse subcutaneous models of cancer harboring tumor-specific endogenous TagRFP red fluorescent protein markers showed a strong increase in fluorescence intensity after applying either a diamagnetic traditional mixture of glycerol/water/DMSO, or paramagnetic compositions containing gadolinium chelate gadobutrol (Gadovist). Subsequent tracking of MR signal intensity changes within selected regions of interest (ROI) located close to the skin surface before, during, and after OC using T2-weighted (T2w) fast spin-echo and T1-weighted gradient-echo pulse sequences enabled the tracking of OC-mediated changes in the skin and underlying tissue. The obtained results pointed to multiple modes of MR image signal-change generation by OC compositions, which are discussed in this chapter. The obtained data suggest that MRI is useful for semi-quantitative monitoring of MR signal intensity time-dependent changes in the subcutaneous space during and after OC, thereby potentially opening the way for the registration of optical and MR signals in the same voxels of live tissue.