Abstract: Polylactic acid microspheres containing spinosad and emamectin benzoate were prepared by solvent evaporation method using central composite design. Influence of content of polylactic acid in oil phase(X1), theoretical pesticide loading(X2) and stirring speed(X3) in the preparation process was investigated. Integrated effect of dependent variables including pesticide loading, entrapment rate, mean diameter, span and release percentage in 5 days was transformed into overall desirability by mathematical method. Data of overall desirabilities were fitted to a second-order polynomial equation, through which three dimensional response surface graphs were described. Optimum experimental conditions were calculated by Design-expert V 8.06. The results indicated that overall desirability increased when content of polylactic acid and stirring speed decreased or when theoretical pesticide loading increased. The highest overall desirability (0.681 1) could be obtained when content of polylactic acid, theoretical pesticide loading and stirring speed were 77.79 mg/mL, 51.06% and 560.91 r/min, respectively. Microspheres prepared according to the optimum experimental conditions resulted in an overall desirability of 0.630 5 while entrapment rate, mean diameter, span, release percentage in 5 days were 84.49%, 7.19 μ m, 1.134, 52.95% respectively. The difference between observed and predicted values of the overall desirability of the optimum formulation was -5.03%. The microspheres were smooth, and the results of DSC showed that pesticides had combined with polylactic acid skeleton properly, which indicated that the mathematical model established in this study could be used to predict the optimized formulation of microspheres containing spinosad and emamectin benzoate.