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Magneto-sensitive (MS) rubber is a kind of smart material, the shear modulus of it can be changed rapidly and reversibly by a magnetic field applied. A smart MS rubber-based isolation system and a nonlinear model based on this MS rubber-based vibration isolation system are developed in this paper. The influence of the amplitude, frequency and magnetic dependency for MS rubber, the mechanical inertance of infinite extended foundation, the mass of solid block and the dimension of MS rubber isolators are all considered in this model. The feasibility of two control strategies aimed at reducing the energy transmitted to the foundation and protecting machine against foundation motion, respectively, is investigated based on this smart vibration isolation system. It is found that compared to the traditional passive rubber isolators, an enhanced vibration isolation effect can be achieved by using MS rubber isolators after control strategies applied. Furthermore, the influence of the amplitude dependency and the response time of MS rubber to the isolation effect is studied. The nonlinear model established for MS rubber isolation system, the control strategies developed and the investigation for the amplitude dependency and the response time of MS rubber to the isolation effect in this paper provide fundamentals for the application of MS rubber in the field of vibration reduction.