OBJECTIVE To optimize the formulation of nicorandil thermosensitive nasal gel (NIC-TNG) and further evaluate its quality. METHODS With gelling temperature and gelling time as observation indexes, the blank formulation composition of NIC-TNG was first optimized by central composite design-response surface method. Franz transdermal diffusion cell method was then used to screen the ideal permeation enhancer by using ex vivo nose mucosa of sheep as test model. The effect of pH on the chemical stability of NIC aqueous solution was investigated to establish the suitable pH of NIC-TNG. Lastly, NIC-TNG was prepared and its main quality items such as the gelation temperature and time, pH, labeled contents of the drug and preservative, cumulative erosion rate, cumulative drug release, and in vitro drug release were studied, respectively. Meanwhile, the effect of temperature on the viscosity, expansion coefficient and water holding capacity of NIC-TNG were investigated. RESULTS The optimized formulation of NIC-TNG consisted of 25 mg·mL^-1 NIC, 172.1 mg·mL^-1 F127, 5.0 mg·mL^-1 F68, 3.8 mg·mL^-1 HPMC, 5.0 mg·mL^-1 chlorobutanol and suitable amount of purified water. The gelation temperature and time, pH, labeled content of NIC and preservative were found to be 30.92 ℃, 40.82 s, 6.42, 99.18% and 98.72%, respectively. There was a good linear correlation between the in vitro cumulative erosion rate, cumulative drug release of NIC-TNG and time (r≥0.999 6). Furthermore, the in vitro release of NIC from the nasal gel showed obvious sustained release characteristics. Temperature exhibited obvious effect on the viscosity of the nasal gel. Finally, NIC-TNG showed low expansion coefficient and good water-holding capacity. CONCLUSION NIC-TNG will be expected to have good clinical application prospects due to its advantages such as reasonable formulation composition, simple preparation process, stable and controllable quality, convenient use and obvious sustained drug release behavior.