BACKGROUND: Biodegradable microspheres are a useful method of drug delivery because they are both injectable and biodegradable. Previous work in our group has characterized implantable preparations of local anesthetics in pellets for prolonged regional anesthesia. In this paper we evaluated injectable suspensions of lidocaine-polymer microspheres for extended period of percutaneous sciatic nerve blockade in rats. METHODS: Microspheres were prepared using poly (lactide-co-glycolide) loaded with 50 wt% lidocaine by a solvent evaporation method. In vitro release rate of lidocaine from microspheres was determined by high performance liquid chromatography (HPLC). Percutaneous blockade of the rat sciatic nerve was performed, and sensory blockade of the nerve was assessed using an analgesiometer. RESULTS: Lidocaine was released in a controlled manner in vitro. In general 60% of the drug released in the first day, 80% in two days. Sciatic nerve blockade duration ranged from 8 to 12 hours. Incorporation of dexamethasone 0.05 wt% into the microspheres resulted in significant prolongation of block. CONCLUSION: Prolonged percutaneous blockade of peripheral nerve is achieved using biodegradable polymeric lidocaine microspheres.