The purpose of this study was to explore the potential application of the combination of microemulsion as a topical delivery vehicle in enhancing the absorption and efficacy of tripterygium wilfordii multiglycoside (TWM). Various microemulsion formulations were developed and an optimal microemulsion (TWM-ME)，which presented spherical droplets and consisted of RH-40, IPM and water was 27: 3.3: 69.7 by weight. It possessd an average droplet size of 23.6 nm, a low viscosity of (3.56±0.12) mm2•s-1 Zeta electric potential was (–5.35±0.42) mV, refractive index was (1.3617±0.0051) nD20, conductivity was (97.6±3.6) μs/cm. Compared to the control solution, TWM-ME provided better skin permeability in vitro. Moreover, TWM-ME has noticeable anti-inflammatory and immune suppression effect. These results indicate that the combination of microemulsion represents an effective vehicle for topical delivery of TWM.