Abstract: During oil and gas field development, permeability is generally considered to be constant, which is not suitable for pressure-sensitive formation. Rock deforms once formation pressure drops, which always makes pore smaller and damages permeability. Mathematic model is studied to describe unstable water injection development for Middle East Paleocene reservoir with characteristics of pressure sensitivity and high difference of formation-saturation pressures. Based on hydrostatics and uniaxial test, Paleocene reservoir core from Middle East region with high difference of formation-saturation pressures is applied for experiment concerning the rule of permeability varying with confining pressure. Moreover, given the assumptions of conventional black oil model, a new mathematical model is set up for deformable-medium reservoir with high difference of formation-saturation pressures by unstable water injection. Research results show that for Middle East Paleocene pressure-sensitive reservoir, permeability has a power-law relationship with formation pressure, permeability decreasing leads to a lower recovery especially at early stage with a largest shrinkage, and unstable water injection is the best development way for this type of reservoir.