Low permeability reservoir has poor physical properties and small pore throat，so it has great seepage resistance in the process of water flooding. It is difficult to establish an effective displacement pressure gradient between injection wells and production wells. It is very important to establish a description method about seepage resistance and study the influencing factors and feature of seepage resistance change of water flooding in low permeability reservoirs. A mathematical model of seepage resistance gradient of the water flooding in the low permeability reservoir was established based on the law of conservation of mass flow of oil and water. The variation feature of the seepage resistance gradient was analyzed by the function of the change rate of seepage resistance gradient，which provides a macroscopic characterization method of seepage resistance gradient of water flooding in low permeability reservoir. Theoretical analysis shows that the seepage resistance gradient shows nonlinear feature in the process of water flooding in low permeability reservoir，which increases first and then decreases with the increase of water saturation. There is a maximum seepage resistance gradient in water flooding of low permeability reservoir，which is related to water injection rate，fluid viscosity and reservoir permeability.The higher the water injection rate，the larger the maximum seepage resistance needs to be conquered；the higher the oil viscosity，the larger the maximum seepage resistance needs to be conquered；the lower the reservoir permeability，the larger the maximum seepage resistance needs to be conquered.