Tumor necrosis factor α (TNFα) is a potent proinflammatory cytokine that plays an important role in immunity and inflammation, in the control of cell proliferation, differentiation and apoptosis. This paper presents a simulation study of the TNFα mediated NF-κB signaling pathway based on a system-theoretic approach. Up to the present, there have been numerous approaches to analyze and model cellular dynamics. The most prominent one is utilizing nonlinear differential equations to establish a mathematical model based on reaction kinetics. This approach can provide us with mathematically well-founded and tractable interpretations regarding pathways, especially those best described by enzyme reactions. This paper introduces not only an intuitive graphical model but also a quantitative mathematical model for the TNFα mediated NF-κB signaling pathway. Throughout simulation study, we can qualitatively validate the developed mathematical model compared with experimental results along this pathway. Further investigations into the TNFα mediated NF-κB signaling pathway are in progress to include an inhibitor kinase functioning in this pathway.