In this article, a series of O-2-[2-(2-methoxyethoxy)ethoxy] acetyl celluloses with different degree of substitution (DS) values was synthesized by a homogeneous reaction of cellulose with 2-[2-(2-methoxyethoxy)ethoxy] acetyl chloride in a 10% (w/w) dimethylacetamide/lithium chloride solution, combined with pyridine as the acid acceptor. The total DS values of the derivatives in anhydroglucose units was determined by H-1 and C-13 NMR spectra, and ranged from 0.4 to 3.0, depending on the amount of acid chloride in the reaction. The effects of the total DS values and the O-2-[2-(2-methoxyethoxy)ethoxy]acetyl acetyl substituent distribution on the solubility of the derivatives were investigated. The lowest limit of the DS value for water-soluble 0-2-[2-(2methoxyethoxy)ethoxy]acetyl cellulose was approximately 0.5, which is lower than that of methylcellulose. The amphiphilic derivatives with higher DS values than 1.7 exhibited a good solubility in both water and organic solvents, such as dimethyl sulfoxide, tetrahydrofuran, and chloroform. Sol-gel transition in aqueous solution was observed for the amphiphilic derivatives with a higher DS value than 1.7; the precipitation temperature (T-p) decreased as the DS value increased, showing that the derivatives are highly temperature sensitive. The thermal properties of the fully substituted derivative were measured using polarized microscopy, DSC, and X-ray diffraction; and are dis cussed in terms of phase transition of the sample derivatives. (C) 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 39: 376-382. 2001.