Cellulose furoate was synthesized via heterogeneous and homogeneous reactions. Cotton cellulose and wood cellulose were used. Lithium chloride/dimethylacetamide solvent was used to dissolve the cellulose for the homogeneous reaction. The esterification reaction between cellulose and 2-furoyl chloride was systematically studied. It revealed that the activation of cellulose was important for its esterification reaction. Activation by solvent exchange decreased the crystallinity and increased the accessibility of cellulose. X-ray diffraction analysis showed no significant change in the spectrogram after activation of cellulose. The degree of substitution of cellulose furoate was influenced by the molecular weight of the cellulose, the stoichiometry of the reagents, the acid scavenger, and the reaction time.