An optimization design method based on 3-D inverse design method and CFD was developed by combining design of experiment method, response surface method and simulated annealing optimization calculation. The method was applied to a centrifugal fan blade design by setting the impeller efficiency and the circulation distribution parameters as the optimization object and the optimization design variables respectively. The efficiency was improved by 2.2% with the optimization method. The effects of the circulation parameters and their interaction effects on the impeller efficiency were analyzed according to the constructed response surface between the design parameters and the impeller efficiency. It is shown that the inlet circulation distribution on the hub plays an important role on the efficiency. Comparing with the hub, the circulation distribution shape on the shroud has more influences on the efficiency.