OBJECTIVE:To optimize the formulation of Curcumin (CUR)transethosomes(CUR-TEs). METHODS :The contents of CUR in CUR-TEs were determined by HPLC. CUR-TEs were prepared by injection method. Using comprehensive score of encapsulation efficiency and drug loading as index ,based on signal factor test ,Box-Behnken design-response surface method was used to optimize and validate the formulation. The property of CUR-TEs prepared by the optimal formulation was investigated. RESULTS:The optimal formulation of CUR-TEs was as follows as lecithin of 4%,CUR of 0.13%,1,2-propylene glycol of 25%,tween-80 of 1%. Results of validation test of optimal formulation showed that comprehensive score of encapsulation efficiency and drug loading of CUR-TEs was 93.04±2.16,relative error of which to predicted value (91.19)was 2.03%. The encapsulation efficiency of CUR-TEs prepared by optimal formulation was (91.17±1.35)%,and its drug loading was (0.94± 0.02)%. The particle size was (190.64±15.97)nm with polydispersity index of 0.086±0.007,and Zeta potential was (-12.74± 1.60)mV. CONCLUSIONS :The optimized formulation of CUR-TEs is stable ,feasible and repeatable ,with good stability.