AIM: To determine the optimized intranasal powders formulation of Panax Notoginseng Saponins(PNS). METHODS: According to the indexes of the in vitro release rate in 1h and 12h of Rb1 and Rg1, bioadhesive intensity and the ciliary toxicity in situtoad palatal mucosa of the preparations, the optimized formulation was determined by the central composite design-response surface methodology. RESULTS: When the correspondent percentage of PNS, microcrystalline cellulose (MCC) and moderate viscosity hydroxypropyl cellulose (H-HPC) was 31%, 60% and 9%, respectively, the release rate in 1h and 12h of Rb1 and Rg1 was 6.82%, 53.25% and 83.4%, 95.09%, respectively. The adhesive time was 78min, and the lasting time of ciliary movement after the rinsing of the PNS powders was 94.84% to the physiological saline group which suggested the powder was almost no toxicity. CONCLUSIONS: The optimized formulation of the PNS intranasal powder was obtained quickly and conveniently by the central composite design-response surface methodology.