OBJECTIVE: To prepare aspirin-β-cyclodextrin-PLGA microspheres, and control its quality. METHODS: Aspirin-β-cyclodextrin inclusion complexes were firstly prepared, and then aspirin-β-cyclodextrin-PLGA microspheres were prepared by emulsion-solvent evaporation method. The morphology and particle size of microspheres were detected, and entrapment efficiency and accumulative release rate were calculated. With entrapment efficiency as index, orthogonal test was adopted to optimize stirring speed, PVA concentration, PVA volume and feed ratio. RESULTS: The optimal formulation was as follows as stirring speed of 4 000 r/min, PVA concentration of 3% (g/100 ml), PVA volume of 30 ml, feed ratio of 1 ∶ 10. Prepared microspheres were round and smooth in appearance. Entrapment efficiency of the microspheres was (41.79±1.09)%. The diameter were regular and ranged 0.5-127.5 μm. As drug-loaded microspheres degraded, the release of aspirin was slow and its accumulative release rate was 83% within 600 h. CONCLUSIONS: Aspirin-β-cyclodextrin-PLGA microspheres are prepared successfully with regular morphology and good sustained-release.