Abstract: OBJECTIVE To prepare the celecoxib loaded microemulsion-based gel and to investigate its transdermal delivery in vitro. METHODS The solubility of celecoxib in different oils, emulsifiers and co-emulsifiers was investigated, and the composition of celecoxib microemulsion was determined by construction of pseudo-ternary phase diagram. By setting the drug loading and particle size as dependent variables while oil, S_mix and water as the independent variables, a D-optimal design method was used to optimize the celecoxib loaded microemulsion. The celecoxib loaded microemulsion-based gel was prepared with Carbomer 980 as a matrix. The microscopic morphology was observed by transmission electron microscopy, and the particle size, size distribution, Zeta potential, transmittance and viscosity were determined. In vitro transdermal release properties were investigated by Franz diffusion cell method. RESULTS The optimized celecoxib loaded microemulsion was composed of 4% oil phase, 20% mixed emulsifier, and 76% water. The average particle size of celecoxib microemulsion-based gel was (59.65±1.09)nm, the PDI was 0.106, and the Zeta potential was (-25.76±0.92)mV. The microemulsion-based gel was round and regular spherical, and the distribution was relatively uniform. Compared with microemulsion, the celecoxib loaded microemulsion-based gel had higher viscosity, which was convenient for spreading and transdermal administration. The cumulative permeation amount within 24 h of the celecoxib loaded microemulsion-based gel was (80.12±3.37)μg·cm^-2, which was significantly higher than that of celecoxib suspension. CONCLUSION The microemulsion-based gel can significantly increase the cumulative transdermal amount of the celecoxib, and is expected to become a novel topical formulation of celecoxib.