Abstract: OBJECTIVE To optimize formulation of PLA-α-asarone nanoparticles(NP) by response surface methodology (RSM). METHODS Plackett-Burman design for independent variables was firstly conducted to prescreen various formulations and process variables during the development of NP. Selected primary variables were further optimized by central composite design. This process lead to an optimum formulation with desired particle size, drug loading and encapsulation efficiency. RESULTS Optimum formulation was as follows:PLA concentration 14.76 mg·mL^-1, α-asarone concentration 4.89 mg·mL^-1, PVA concentration 1% and volume ratio of oil-water 1:2. These prepared PLA-α-asarone nanoparticles had round surface and uniform size with average particle size of 265.4 nm, PDI index of 0.038, drug loading efficiency of 12.40% and encapsulation efficiency of 55.86%, relative errors of these parameters were small by comparing with the bias values. CONCLUSION The study demonstrates the feasibility that response surface methodology can be used to optimize the formulation and process variables to achieve favorable responses for PLA-α-asarone nanoparticles.