The vertical stiffness of laminated rubber bearings degrades with the increase of shear deformation under earthquake, and the influence on the isolated structure is not yet clear. Therefore, several isolated frame structure models with different floor numbers, floor heights, and column distances were established by ABAQUS. The modified two-spring model was adopted for the bearings, and a program considering the vertical stiffness degradation of bearings was developed by FORTRAN language based on the model and user subroutine interface UEL in ABAQUS. Then rare earthquakes were input and the elastic-plastic dynamic time history analyses were carried out. Influences of vertical stiffness degradation on structural response were studied. Results show that the vertical stiffness degradation of bearings had certain effects on the shear force, axial force, bending moment of column, and bending moment of beam, and the seismic response amplification factors ranged from 1.1 to 1.3. The vertical stiffness degradation of bearings had no obvious influence on the shear deformation of the bearings or the interlayer displacement of the structures. This study provides a reference for future calculation and analysis of isolated structures under rare earthquakes.