Which was mimicked by changing the interval of pulsatile TNFa stimulation, resulted in different gene expression patterns. Thus, it is thought that the oscillation pattern of nuclear NF-kB is important to the selection of expressed genes. According to experimental observations on the oscillation of nuclear NF-kB, nearly 40 computational models have been published. Among them, a model by Hoffmann et al. was the first to show the oscillation of nuclear NF-kB in computer simulation. Their computational model included continuous activation of IKK, degradation of IkBa, shuttling of NF-kB between the cytoplasm and nucleus, and NF-kB-dependent gene expression and CT99021 GSK-3 inhibitor protein synthesis of IkBa. Their simulations showed good agreement with experimental observations. After Hoffmann’s model, many models have been published showing the effect of A20, a negative regulator of NF-kB, IkBe or IkBd, other inhibitors of NF-kB, phosphorylation and dephosphorylation of IKK, and IKK-dependent and independent degradation pathways for IkBa. Characterization of oscillation and sources of cell-to-cell variability of oscillation were also reported. Recently, a possible role of the oscillation of nuclear NF-kB as the decision maker for the cell fate by counting the number of oscillations was proposed. None of these models are complicated, yet it is not easy to explain the essential mechanism of oscillation. There is a report on simplified computational models showing the minimal components of the oscillation of nuclear NF-kB. This analysis showed essentially the same mechanism of oscillation that was reported previously in more abstracted forms. Thus the oscillation of nuclear NF-kB is a good example of collaboration between in vitro and in silico experiments. However, all computational models shown above are temporal models and include no discussion on spatial parameters such as diffusion coefficient, nuclear to cytoplasmic volume ratio, nor the location of protein synthesis within the cytoplasmic compartment. In contrast to these temporal models, a two-dimensional model was published showing that changes in the geometry of the nucleus altered the oscillation pattern of nuclear NF-kB. However, a three-dimensional model is important to compare its simulation results reasonably with observations. Here we construct a 3D model, and investigate the oscillation patterns of nuclear NFkB by changing spatial parameters. First we find that the parameters used in the temporal model must be changed in the 3D model to obtain the observed oscillation pattern. Second, spatial parameters strongly influence oscillation patterns. Third, among them, N/C ratio strongly influences the oscillation pattern. Fourth, nuclear transport, which would be changed by the increase or decrease of nuclear pore complexes, also has a strong effect on changes in the oscillation pattern. In summary, our simulation results show that changes in spatial parameters such as the N/C ratio result in altered oscillation pattern of NFkB, and spatial parameters, therefore, will be important determinants of gene expression. The oscillation frequency was calculated from the distance between the first and the second peaks. Simulation results showed that any combinatorial changes of these spatial parameters were unable to generate an oscillation frequency that agrees with the temporal observation. These simulation results indicate that rate constants used in the temporal model should be changed in the spherical 3D cell model.