The results of an experimental program on eight short reinforced concrete columns having different structural sizes and axial compression ratios subjected to monotonic/cyclic lateral loading were reported. A 3D mesoscopic simulation method for the analysis of mechanical properties of reinforced concrete members was established, and then it was utilized as an important supplement and extension of the traditional experimental method. Lots of numerical trials, based on the restricted experimental results and the proposed 3D mesoscopic simulation method, were carried out to sufficiently evaluate the seismic performances of short reinforced concrete columns with different structural sizes and axial compression ratios. The test results indicate that (1) the failure pattern of reinforced concrete columns can be significantly affected by the shear-span ratio; (2) increasing the axial compression ratio could improve the load capacity of the reinforced concrete column, but the deformation capacity would be restricted and the failure mode would be more brittle, consequently the energy dissipation capacity could be deteriorated; and (3) the load capacity, the displacement ductility, and the energy dissipation capacity of the short reinforced concrete columns all exhibit clear size effect, namely, the size effect could significantly affect the seismic behavior of reinforced concrete columns.