A mechanism of cellulose phosphorylation in presence of urea is proposed. This model is correlated with the thermal stability of phosphorylating reactive mixture and the yield of phosphorylation for two different reagents: phosphoric acid and lauryl phosphate monoester. Three main successive reactions are involved in the formation of cellulose phosphate: (1) generation of ammonia by urea decomposition, (2) formation of phosphoramidate as intermediate reactive due to the reaction of ammonia with phosphate species, and (3) grafting the phosphate moiety to substrate due to the transfer of phosphate from phosphoramidate to cellulose. The proposed in vitro mechanism is supported by similar phosphorylation processes observed in some biochemical reactions. The limiting factor in the phosphorylation of cellulose is the formation of phosphoramidate intermediate.