Objective      To optimize and assess the preparation of self-microemulsifying drug delivery system (SMEDDS) for puerarin.       Methods      Compatibility of prescriptions was tested by measuring the solubility of puerarin in different secondary solvents. Components of puerarin SMEDDS were screened by plotting pseudo-ternary phase diagram. According to the balanced solubility and particle size of puerarin in different self-microemulsifying drug prescriptions

the optimal prescription was determined using the central composite design-response surface methodology. The nature of puerarin in SMEDDS was studied by diffusing the dialysis bag.       Results      The optimal prescription of puerarin in SMEDDS was composed of ODO (oil)

Cremophor RH40 (surfactant)

and Transcutol P (co-surfactant)

with a weight ratio of 17.5∶55.0∶27.5. The solubility of puerarin in the optimal prescription was 51.27 mg/g

which was 9.22 times of that in distilled water. The average particle size was 21.51 nm. The release of puerarin was faster from SMEDDS than from puerarin suspension.       Conclusion      The successfully prepared puerarin SMEDDS can significantly increase the solubility of puerarin. An optimal prescription for puerarin in SMEDDS can be quickly and conveniently achieved using the central composite design-response surface methodology．