The gelation process of methylcellulose (MC) in light (H2O) and heavy (D2O) waters was investigated using NMR and DSC to elucidate solvent isotope effect on the process. As temperature is raised, MC chains in both solvents undergo the aggregation and subsequent gelation; however, their onset temperatures are lower in D2O than H2O. This demonstrates that D2O enhances the hydrophobic attractive force, which is the driving force for the aggregation and gelation. We propose that the excluded volume effect of the hydrophobic segments in MC chains should play a pivotal role for the enhancement, while, prior to the above investigation, chemical shift assignments of proton and carbon resonances are performed, and six resonances are newly assigned.