An amphoteric cellulose derivative, O-carboxymethyl-O-2-hydroxy-3-(trimethylammonio) propylcellulose (CM-HTMAPC), was prepared by the etherification of O-carboxy-methylcellulose (CMC) with (3-chloro-2-hydroxy-n-propyl)-trimethylammonium chloride in a NaOH solution. Apparent molecular sizes of the amphoteric cellulose derivative in aqueous solutions of different NaCl concentrations under various pH conditions were investigated by gel permeation chromatography (GPC), and results were evaluated in terms of inter- and intramolecular ionic interactions. Relation between GPC and viscosity results was also discussed. A titration method to determine the apparent acidic dissociation constants of carboxymethyl substituents was developed and the effect of cationic substituents on apparent acidic dissociation constants was examined.