Chitosan (CS) gel beads were prepared in 10% amino acid solution (pH 9) and modified by forming an electrostatic complex between the amino group of CS and the carboxyl group of chondroitin sulfate (Cho). Modification of the CS gel matrix by Cho inhibited the in vitro release of prednisolone (PS) from the gel beads. CS gel beads modified by Cho (CS-Cho) were implanted into air pouches (AP) prepared subcutaneously on the dorsal surfaces of mice. No inflammatory response was observed. The in vivo release of PS from CS-Cho gel beads and their biodegradation in the AP was slower than beads without Cho treatment. After 28 days of implantation, CS-Cho gel beads (deacetylation of CS: 90%) were still detectable, although they had become softer and smaller. Modification of the CS gel matrix by Cho controls the biodegradation of the beads and the release of the drug. This effect makes these beads a promising biocompatible and biodegradable vehicle for sustained drug delivery.