Experimental evidence indicates that the biosynthetic activity of chondrocytes is associated with the mechanical environment. For example, excessive, repetitive loading has been found to induce cell death, morphological and cellular damage, as seen in degenerative joint disease, while cyclic, physiological-like loading has been found to trigger a partial recovery of morphological and ultrastructural aspects in osteoarthritic human articular chondrocytes. Mechanical stimuli are believed to influence the biosynthetic activity via the deformation of cells. However, the in situ deformation of chondrocytes for cyclic loading conditions has not been investigated experimentally or theoretically. The purpose of the present study was to simulate the mechanical response of chondrocytes to cyclic loading in unconfined compression tests using a finite element model. The material properties of chondrocytes and extracellular matrix were considered to be biphasic. The time-histories of the shape and volume variations of chondrocytes at three locations (i.e., surface, center, and bottom) within the cartilage were predicted for static and cyclic loading conditions at two frequencies (0.02 and 0.1 Hz) and two amplitudes (0.1 and 0.2 MPa). Our results show that cells at different depths within the cartilage deform differently during cyclic loading, and that the depth dependence of cell deformation is influenced by the amplitude of the cyclic loading. Cell deformations under cyclic loading of 0.02 Hz were found to be similar to those at 0.1 Hz. We conclude from the simulation results that, in homogeneous cartilage layers, cell deformations are location-dependent, and further are affected by load magnitude. In physiological conditions, the mechanical environment of cells are even more complex due to the anisotropy, depth-dependent inhomogeneity, and tension-compression non-linearity of the cartilage matrix. Therefore, it is feasible to speculate that biosynthetic responses of chondrocytes to cyclic loading depend on cell location and load magnitude.