Tramadol HCl(TH)-loaded poly(L-lactide-co-glycolide)(PLGA) microspheres were prepared by O/O solvent evaporation method for sustained release. We investigated the release behavior according to PLGA molecular weight and concentration. TH-loaded PLGA microspheres were characterized on the surface and cross-section morphology by SEM. TH-loaded PLGA microspheres had smooth surfaces and various pores in internal structure. As the PLGA molecular weight and PLGA concentration increased, the release rate of TH decreased. The behaviors of degradation was decreased according to increased PLGA molecular weight. These results showed that the release behaviors can be controlled by various of molecular weight and concentration of PLGA.