© 2019 American Chemical Society. Cellulose I fibrils swell on exposure to ethylenediamine (EDA), which forms the cellulose I-EDA complex. These are regarded as host materials with guest intercalation. The present study reports molecular dynamics (MD) simulations of cellulose I-EDA crystal models with finite fiber to reproduce desorption of EDA molecules. The force field parameters for EDA were improved. Part of the EDA molecules was desorbed only from the surfaces of the crystal models, not from their interiors. The EDA molecules diffused through a hydrophilic channel composed of the hydrophilic edges of the cellulose chains, and their conformations and orientations changed. With the configuration of the cellulose chains being held, the vacant hydrophilic channel was immediately filled with water molecules. The innermost part of the crystal models, defined as a core unit, was partly deformed from the initial crystal structure, including the changes in the exocyclic group conformations of the cellulose chains and the orientations of the EDA molecules, coupled with partial reconfiguration of the intermolecular hydrogen bonding scheme. A possible crystalline conversion scheme after complete desorption of EDA has been discussed based on the present findings.