Immunophilin ligand FK506 has been treated as adjunct therapy for nerve repair due to its potent neurotrophic and neuroprotective actions. It was hypothesized that FK506 releasing from biodegradable chitosan guide provided better nerve regenerative response than the guide with no FK506. The drug was entrapped in the semi-permeable wall of chitosan guide with the drug-loading of 647 mu g/g. Rat sciatic nerve defect model treated with FK506-releasing chitosan guide showed more mature appearance of myelinated fibers 8 weeks after surgery; furthermore, the motor functional reinnervation occurred, the amplitude and velocity of compound muscle action potentials reached 60% and 73% with respect to the normal. Thus, FK506-releasing chitosan guide should be acted as a long-lasting delivery device of immunosuppressive and neuroregenerative agent for peripheral nerve repair.