OBJECTIVE: To optimize the purification technology of total flavones from Ampelopsis grossedentala with macroporous resins. METHODS: 4 kinds of macroporous resins for the purification of total flavones from A. grossedentala were screened by using drug-loading amount, desorption rate, recovery and purification rate as indicators. Single factor test and central composite design-response surface methodology were used to optimized eluant mass fraction, adsorption time, flow rate of eluant, eluant pH and other factors of purification technology, and validation test was also conducted. RESULTS: D-101 macroporous resin was the best. The optimal condition was as follows as the concentration of sample solution 2 mg (by extract weight)/ml, the volume of sample solution 1.1 BV, ethanol 86.0%, adsorption time 36.7 min, flow rate of eluant 3.81 BV/h, pH 7. In validation test, mass fraction of total flavones increased from 66.83% to 85.00% in validation test (RSD=0.15%, n=3), and were close to predicted value (85.08%). CONCLUSIONS: Central composite design-response surface methodology is feasible and stable for the optimization of purification technology of total flavones from A. grossedentala with macroporous resins.