OBJECTIVE: To optimize the formulation of rare ginsenoside Compound K (CK) mixed micelle, and to investigate its in vitro release and apparent permeability coefficients (Papp). METHODS: Using soy lecithin and vitamin E polyethylene glycol 1 000 succinate (TPGS) as excipients, CK mixed micelle was prepared by solvent evaporation method. Using drug-loading amount, encapsulation efficiency and particle size as index, orthogonal test was adopted to optimize feeding amount, the ratio of granulesten to TPGS and hydration volume; the micelle prepared by optimal formulation was investigated in respects of form, particle size, drug-loading amount, encapsulation efficiency, solubility, in vitro release; Papp of colon adenocarcinoma Caco-2 cell model was also inspected. RESULTS: The optimal formulation was as follows as feeding amount 1.0 mg, the ratio of granulesten to TPGS 1 ∶ 1, hydration volume 10 ml. The mixed micelles were spherical or spheroidal; the average particle size was (110±2.69) nm, and drug-loading amount was (4.32±0.19)%, entrapment efficiency was (92.23±2.76)%, and average solubility was (469.21±0.024) μg/ml; 150 h accumulative release rate was (66.19±0.027)% (n=3). Papp of CK crude drug and CK mixed micelle were 26.20 and 3.78 (n=6). CONCLUSIONS: The optimized preparation technology is feasible, and CK mixed micelle is prepared successfully.