The phenomenon of the change of physical parameters in reservoir rock owing to the change in effective stress is called the stress sensitivity of reservoir rock. During drilling and exploitation, this change will result in irreversible close in rock's pores and fractures, and reduce productivity directly. The conventional experiment of stress sensitivity is conducted at room temperatures by altering the confining pressure of laboratory cores. Combining the experimental data with the microstructure of rocks obtained by cast thin section and Mercury-Injection method, this paper investigates the permeability sensitivity characteristics of low-permeability reservoirs and the relationship between microstructure and stress sensitivity. The functional relationship between permeability and effective stress is established providing experimental basis for the research and applications of the reservoir rock stress sensitivity.