To achieve sustainable development of construction industry, the application of HRB500 reinforcement with high strength and high ductility in RC structures is being promoted in civil and structural engineering in China. But few studies focus on seismic behaviors of RC structures reinforced with HRB500 bars. In this analysis, three RC frame structures on the Zone of Fortification Intensity 8 (0.3g) in China reinforced with HRB500, HRB400 and HRB335 bars respectively, are designed confirming to the latest draft of the revising Code for the Design of Concrete Structures. Then inelastic seismic response analyses of the three frames with multiple inputs of ground motions are conducted. The seismic response rules and seismic performances of the RC frame reinforced with HRB500 bars are compared with those frames reinforced with HRB400 and HRB335 bars. The analytical results indicate that under ground motions in rare earthquake level, the maximum displacements of the frame reinforced with HRB500 bars are roughly the same as those of the frames reinforced with HRB400 and HRB335 bars, while the rotation ductility demand of elements in the former structure is smaller than those of elements in the latter structures. It is also found that the frame reinforced with HRB500 bars develops a plastic energy dissipation mechanism that is dominated by beam hinges under major earthquake, and the maximum interstorey drift of the frame can satisfy the requirement in the Code for the RC Frame Structures.