In this work, the carboxymethylation of cellulose in a new alkaline cellulose solvent, LiOH/urea aqueous solution, was investigated. Carboxymethyl cellulose (CMC) samples were characterized with FT-IR, NMR, HPLC, and viscosity measurements. Water-soluble CMC with DS = 0.36∼0.65 was prepared, from both Avicel cellulose and cotton linters in the LiOH/urea system. The total DS of CMC could be controlled by varying the molar ratio of reagents and the reaction temperature. The results from structure analysis by HPLC after complete depolymerization showed that the mole fractions of the different carboxymethylated repeating units as well as those of unmodified glucose follow a simple statistic pattern. A distribution of the carboxymethyl groups of the AGU was determined to be in the order O-6 > O-2 > O-3 position at the level.