Objective：To prepare ginsenoside Rg3-loaded chitosan microspheres for intranasal administration.Methods: The chitosan microspheres were prepared by the O/W/O combined with multiple emulsification chemical crosslink technique.Quadratic polynomial equation and linear regression equation were fitted by the statistic software,and the resulting equations were used to produce response surface graphs.The best experiment conditions were screened by central composite design (CCD) using drug load,encapsulation efficiency,and the proportions of microspheres (with diameter of 40-60 μm) as variables.The shape of microspheres was observed by scanning electron microscope.Results: The best ranges of the prescription included:drug to carrier material ratio:0.4-0.5;organic phase and water phase ratio:0.4-0.6;and first emulsion and oil phase ratio:0.13-0.17.The 3 batches of microspheres prepared according to the above condition were well-shaped (full sphere),with the mean drug loading capacity being (10.25±0.08)% and the encapsulation efficiency being (30.61±1.46)%.Conclusion: The optimized technique has a good reproducibility and can be used for preparation of Rg3-loaded chitosan microspheres for intranasal administration.