Recently, considerable interest has been focused on the use of biodegradable polymers for specialized applications such as controlled release of drug formulations; meanwhile, microsphere drug-delivery systems using various kinds of biodegradable polymers have been studied extensively during the past two decades. Poly (lactide-co-glycolide) (PLGA) polymers have been proven to be excellent drug carriers for microparticulate systems due to their advantages, e.g. biocompatibility and regulatory approval. The administration of nonsteroidal anti-inflammatory drugs (NSAIDs) into the intra-articular cavity in patients with chronic inflammatory disease is complicated due to the short duration of effect. In the present study, controlled-release parenteral formulations of diclofenac sodium (DS), a commonly used NSAID, were prepared for intra-articular administration, and evaluated in vitro for particle size, yield, drug loading, surface morphology and release characteristics. For in vivo studies, Technetium-99m labelled polyclonal human immunogammaglobulin (^99m Tc-HIG) was used as the radiopharmaceutical to demonstrate arthritic lesions by gamma scintigraphy. Evaluation of arthritic lesions post-therapy in rabbits showed no significant difference in the group treated with PLGA (50:50) (mw 34 000) DS microspheres compared to control groups.