OBJECTIVE： To optimize the preparation technology of Andrographolide self-microemulsion. METHODS： The types of emulsifier， co-emulsifer and oilphase were screened with appearance， color of them in water phase as indexes. The amount range of each matrix was screened by using pseudo-ternary phase diagram. The preparation technology of Andrographolide self-microemulsion was optimized by Box-Behnken response surface technology with particle size， dispersion index and equilibrium solubility as evaluation indexes， comprehensive score as response value， using mass fraction of emulsifier， mass fraction of co-emulsifier and mass fraction of oil phase as response factors. RESULTS： The optimal preparation technology of Andrographolide self-microemulsion included that polyoxyethylene hydrogen sesame oil as emulsifier， diethylene glycol mono ethyl ether as emulsifier， oleic acid polyethylene glycol glyceride as oil phase， with weight ratio of 40 ∶ 59 ∶ 10. Under the condition， particle size of obtained self-microemulsion was （38.15±1.56） nm， dispersion index was 0.12±0.01 and equilibrium solubility was （5.97±0.02） mg/mL， relative error of which to predicted value （39.72 nm， 0.11， 6.04 mg/mL） were 3.95％， 3.54％， 1.16％. The measured value was in good agreement with the predicted value. CONCLUSIONS： The optimal Andrographolide self- microemulsion is stable， feasible and suitable for the preparation of the self-microemulsion.