This research synthesized graft copolymers of chitosan-g-poly(N-isopropyl acrylamide) (CS-g-PNIPAAm) by UV-initiated free-radical polymerization of NIPAAm monomer to CS selectively at the C-6 position of pyranose ring. First, amino groups in CS were protected by reaction with phthalic anhydride (PA) to form PACS. The degree of phthaloylation was carefully controlled to ensure that most amino groups were protected, and only a very small amount of hydroxyl groups were reacted. In the second step, the vinyl functional group was introduced to the PACS by reaction with a vinyl compound containing an isocyanate group (3-isopropenyl-alpha alpha'-dimethylbenzyl isocyanate), through the urethane linkage with hydroxyl groups at the C-6 position. The phthaloyl groups were then removed by hydrazine to recover the amino groups in CS. Finally, PNIPAAm was grafted to the vinyl CS at the C-6 position by UV-initiated free-radical polymerization. The synthesized CS-g-PNIPAAm copolymers were confirmed to have a structure of an AB-crosslinked graft copolymer. Respectively, these copolymer hydrogels exhibited pH-and thermal-responsive swelling properties in an aqueous solution due to their CS and PNIPAAm components. The test of cell viability with L929 fibroblast revealed that the CS-g-PNIPAAm copolymers having a grafting ratio lower than 1.7 had cellular compatibility as good as pure CS. (C) 2010 Wiley Periodicals, Inc. J Appl Polym Sci 120: 1-12, 2011