In order to study the development of the delivery device of long-acting local anaesthetics for post-operative analgesia and control of chronic pain of cancer patient, fentanyl loaded poly( l -lactide- co -glycolide) (PLGA, molecular weight; 5000, 8000, 20 000, and 33 000 g/mole) microspheres (FMS) were studied. FMS were prepared by an emulsion solvent-evaporation method. The influence of several preparation parameters such as initial drug loading, PLGA concentrations, emulsifier concentrations, oil phase volume and mole ratio and molecular weight has been investigated on the fentanyl release patterns. Generally, the drug showed the biphasic release patterns, with an initial diffusion followed by a lag period before the onset of the degradation phase, but there were no lag times in the device. Fentanyl was slowly released from FMS over 10 days in vitro , with a quasi-zero order property. The release rate increased with increasing drug loading as well as increasing polymer concentration with a relatively small initial burst effect. From the results, FMS may be a good formulation to deliver the anaesthesia for the treatment of chronic pain.