Based on a three-story RC frame, the analysis of the structure with various layouts of infill walls under frequent earthquake was conducted. The results indicate that when the infill walls and their different layouts are incorporated into the structural model, the seismic performance, such as dynamic properties, characteristics of regularity, and internal force distributions would change significantly. It should be also mentioned that because of the constraint of infill walls, the sum of moments at column ends is much larger than that at beam ends at the frame column-beam joints. It is suggested that infill walls should be adequately considered in the mechanical models during seismic analysis.