OBJECTIVE To optimize the preparation process of sinomenine microemulsion and evaluate its pharmacodynamics.METHODS HPLC method for sinomenine content determination was established,and sinomenine microemulsion prescription was in-itially screened by solubility test and pseudo-ternary phase diagram.D-optimal mixing experimental design method was used to optimize sinomenine microemulsion prescription with particle size and drug load as investigation indexes,and its particle size,drug load and sta-bility were evaluated.Transdermal absorption was investigated by transdermal test in vitro,and the anti-inflammatory effect was evalua-ted by ear swelling test.RESULTS With methanol:0.1%phosphoric acid(40 ∶ 60)as the mobile phase,the detection wavelength was 262 nm,and the method was suitable for the determination of sinomenine.The optimal formula of microemulsion was obtained as castor oil(7.0%),PEG40 hydrogenated castor oil/anhydrous ethanol(69.0%),the optimal Km value was 3∶1,and distilled water(24.0%).The average particle size of the microemulsion was 18.76 nm,the PDI was 0.072 and the drug loading was 5.225%.The cumulative permeability of 1.0%sinomenine microemulsion at 12 h was 1.223 4 μg·cm-2,and the steady permeability rate was 0.0649 μg·cm-2·h-1,which was better than sinomenine solution.The inhibitory rate of sinomenine microemulsion was 65.07%,which was similar to dexamethasone.CONCLUSION The preparation of sinomenine microemulsion has the advantages of stable process,high drug loading,good transdermal absorption and anti-inflammatory effect,which can provide reference for the development of sinomenine transdermal drug delivery preparation.