Triptolide possesses immunosuppressive, anti-fertility and anti-cancer activities. Due to its severe toxicity, microemulsions with controlled, sustained and prolonged delivery of triptolide via a transdermal route are expected to reduce its adverse side effects. The purpose of the present study was to investigate the microemulsions for transdermal delivery of triptolide. The pseudo-ternary phase diagrams were developed and various microemulsion formulations were prepared using oleic acid as an oil, Tween 80 as a surfactant and propylene glycol as a cosurfactant. The droplet size of microemulsions was characterized by photocorrelation spectroscopy. The transdermal ability of triptolide from microemulsions was evaluated in vitro using Franz diffusion cells fitted with mouse skins and triptolide was analyzed by high-performance liquid chromatography. The effect of menthol as a permeation enhancer, and the loading dose of triptolide in microemulsions on the permeation rate were also evaluated. The triptolide-loaded microemulsions showed an enhanced in vitro permeation through mouse skins compared to an aqueous solution of 20% propylene glycol containing 0.025% triptolide. The permeation of microemulsions accorded with the Fick's first diffusion law. No obvious skin irritation was observed for the studied microemulsion ME6, but the aqueous solution of 20% propylene glycol containing 0.025% triptolide revealed the significant skin irritation. The results indicate that the studied microemulsion systems, especially ME6, may be promising vehicles for the transdermal delivery of triptolide.