OBJECTIVE: To study the pharmacokinetics and brain targeting of Toutongning nasal spray in rats in vivo. METHODS: 84 SD rats were divided into nasal administration group and vein administration group, 42 in each group, with dose of 1.2 mL/kg. 5 mL sample blood was taken in abdominal aorta after 5, 10, 15, 30, 60, 90, 120 min of administration, and brain tissue was taken (6 rats in each time point). HPLC-MS was adopted to determine the concentration of prim-o-glucosylcimifugin and 5-O-methylvisammioside in plasma and brain tissue of rats in each group, and DAS 2.0 software was used to calculate the pharmacokinetic parameters and brain targeting indexes. RESULTS: The cmax of prim-o-glucosylcimifugin and 5-O-methylvisammioside in plasma of rats in nasal administration group were (0.202 4±0.015 8), (0.373 8±0.085 7) μg/mL; tmax were (10.000 0±0.000 0) min; and AUC0-∞ were (16.542 9±2.110 3), (27.452 7±5.572 1) μg·h/mL, respectively. The cmax of prim-o-glucosylcimifugin and 5-O-methylvisammioside in brain tissue of rats were (0.180 2±0.038 4), (0.320 4±0.027 7) μg/g; tmax were (10.000 0±0.000 0) min; and AUC0-∞ were (17.105 3±2.432 9), (24.541 6±3.753 4) μg·h/g, respectively. The cmax of prim-o-glucosylcimifugin and 5-O-methylvisammioside in plasma of rats in vein administration group were (0.300 2±0.016 1), (0.526 7±0.044 1) μg/mL; tmax were (10.000 0±0.000 0) min; and AUC0-∞ were (28.010 5±4.112 8), (60.294 1±11.290 2) μg·h/mL, respectively. The cmax of prim-o-glucosylcimifugin and 5-O-methylvisammioside in brain tissue of rats were (0.149 8±0.031 5), (0.199 8±0.040 1) μg/g; tmax were (15.000 0±0.000 0) min; and AUC0-∞ were (22.643 4±2.883 1), (36.721 8±14.885 6) μg·h/g, respectively. The brain targeting indexes of prim-o-glucosylcimifugin and 5-O-methylvisammioside were 2.387 0 and 2.176 1, respectively. CONCLUSIONS: After nasal administration of Toutongning nasal spray, parts of drugs can directly transport to the brian by nasal absorption. It is scientific and reasonable to make nasal spray.