This work is focused on the development of a new injectable drug delivery system for proteins sustained release. A series of in situ forming hydrogels derived from oxidized carboxymethylcellulose (OCMC) and N-succinyl-chitosan (NSC) were prepared by Schiff base reaction. OCMC was prepared by cleaving the vicinal glycols in carboxymethylcellulose with sodium periodate and NSC was obtained by introduction of succinyl groups into chitosan N-terminal of the glucosamine units, respectively. The gelation readily took place at physiological pH and temperature. Several parameters, such as matrix gelation time, equilibrium swelling ratio, matrix degradation rate and drug release profile, were investigated. The in vitro cytotoxicity studies showed that the OCMC/NSC hydrogels were non-cytotoxic and preserved the viability of the entrapped cells. The release profile of BSA was divided into four stages, indicating that the release of BSA was controlled by both diffusion and degradation. Importantly, activity of released BSA was retained regardless of the oxidation degree. This newly described OCMC/NSC hydrogels demonstrated attractive properties and would be a suitable injectable and biodegradable system for the delivery of protein drugs. (c) 2010 Elsevier B.V. All rights reserved.