OBJECTIVE： To prepare Usnic acid self-microemulsion， prescription optimization and evaluate its quality. METHODS： Usnic acid self-microemulsion was prepared by emulsification method using medium chain triglycerides-single linoleic acid glyceride （1 ∶ 1， m/m） as oil phase， polyoxyethylene hydrogenated castor oil as emulsifier， diethylene glycol monoethyl ether as co-emulsifier. Based on the solubility test and pseudotemary phase diagram， using self-emulsifying time （t）， light transmittance （T）， drug equilibrium solubility （S）， accumulative dissolution rate at 5 min and 60 min （Q5 min， Q60 min） as evaluation indexes， central composite design-response surface methodology was utilized to optimize oil phase ratio and ratio of emulsifier to co-emulsifier （Km） in microemulsion formulation. At the same time， the optimal formulation was verified， the morphology， particle size， drug-loading amount and dissolution of Usnic acid self-microemulsion were investigated. RESULTS： The optimal formulation was as follows as oil phase ratio of 25％， Km of 2.0； ratio of mixed oil phase， emulsifier， co-emulsifier in the formulation was 25％， 50％， 25％. t， T， S， Q5 min and Q60 min of Usnic acid self-microemulsion prepared by optimal formulation were 1.96 min， 87.67％， 5.67 mg/g， 66.58％， 76.73％ （all RSD＜3％， n＝3）， respectively. The relative errors of them to predicted values were all less than 4％ （n＝3）. Usnic acid self-microemulsion was spherical droplet in shape after diluted with water. The average particle size was 39.4 nm， average drug-loading amount was 4.55 mg/g. Q90 min of Usnic acid self-microemulsion reached 99.58％ in pH 6.8 phosphate buffer （n＝3）. CONCLUSIONS： Prepared Usnic acid self-microemulsion is in line with quality requirements.