The establishment of an effective finite element model (FEM) for the bridge structure is essential in the health monitoring system of urban grade separation bridge. It inevitably exist inconsistency of response between the FEM and practical structure due to various uncertain factors in the modeling and analysis procedure. Therefore the updating of FEM is necessary. A uniform design-based static model updating method is proposed in this paper, the allowable range of model parameters (the number is ) is divided into several levels (the number is ), the model updating method is transformed into a -factors and -levels test design. Several groups of combined parameters are selected to conduct test through finite element calculation based on the principle of uniform design method, and the optimal parameter group is obtained. This method is applied to the model updating of a complicated special-shaped urban grade separation bridge, and a perfect FEM with a good agreement with measured data is obtained. It confirms the feasibility and superiority of this method.