The in vivo decomposition of regenerated cellulose in the digestive organs of a mouse was investigated for the first time, in anticipation of food products of regenerated cellulose becoming commercially available. In past studies, plants were grown from their seeds in a labeled CO2 environment and labeled cellulose was then extracted from these plants. The small amounts of the obtained labeled cellulose made the study of in vivo decomposition of cellulose in a digestive tract difficult. In the present study, a new method was developed to overcome this. 13C-labeled natural cellulose (13C-NC) was produced from cultures of Gluconacetobacter xylinus supplemented with 13C-labeled glucose. 13C-labeled regenerated cellulose was then prepared from a hydrolyzed 13C-NC/aqueous cuprammonium solution. 13C NMR revealed that the labeling ratio of 13C to 12C in 13C-labeled cellulose was 48.3% (mol/mol). The degree of in vivo decomposition is defined as the ratio of 13C in 13CO2 in the expired gas from mice to 13C in 13C-labeled cellulose fed to the mice. Although the decomposition rate for regenerated cellulose by enzymatic saccharification was markedly higher than that for natural cellulose under in vitro conditions, the decomposition of regenerated cellulose by mice was similar to that for natural cellulose under in vivo conditions, with decomposition rates of 18.1% (w/w) for regenerated cellulose and 15.4% (w/w) for natural cellulose. These results suggest the potential of regenerated cellulose as a low-calorie food material similar to natural cellulose.