Water soluble cellulose ethers, including methylcellulose and two hydroxyethylcelluloses with different molecular weights, were conjugate with indomethacin at room temperature. The chemical structures of the conjugates were characterized by FTIR. (1)H NMR and UV-vis spectroscopy. The results confirmed that different amounts of IND residues were covalently bonded to cellulose ether backbones through ester linkages. Their anaerobic biodegradation in colonic fermentation was investigated by gel permeation chromatography, gas chromatography and UV-vis spectroscopy. These conjugates were found to have different biodegradabilities, depending on the cellulose ether used and the amount of conjugated indomethacin residues. In vitro release experiments showed that hydroxyethylcellulose-based conjugates with low IND residues content could exhibit a sustained drug release behavior in colonic fermentation and were stable in the simulated media of the stomach and small intestine. Therefore, they are promising candidates for future applications in colon-specific drug delivery. (C) 2009 Elsevier Ltd. All rights reserved.