Stress sensitivity occurs throughout the reservoir development process, especially in the study of low permeability tight reservoir, considering the influence of stress sensitivity is particularly important. When studying stress sensitivity, the current main experimental methods are variable confining pressure and variable fluid pressure methods, but they cannot simulate the stress sensitivity during water injection development. Therefore, in this paper, an experimental stress sensitivity method that can be used to study the depletion mining and water injection development processes is established. In addition, the influence of different degrees of microcrack development on the stress sensitivity of the reservoir is investigated. The results of this study show that under the experimental conditions described in this article, the loading of axial compression plays a role of preloading stress and realizes the whole process of stress sensitivity under the condition that the fluid pressure is lower than the confining pressure. In the experiment, the permeability growth rate of matrix cores does not exceed 20%. For cores containing microcracks, when the axial pressure was less than 30 MPa, the permeability slowly increased with increasing fluid pressure. When the axial pressure was 30 MPa, the permeability changes are mainly divided into two stages. In the first stage, the microcracks are closed under compressive stress. At this time, the microcracks have a limited impact on the seepage capacity. The permeability increases slowly with increasing fluid pressure. In the second stage, the permeability rapidly increases after the microcracks open. These two stages can be described by two straight lines. The slope of the first line has nothing to do with the development of microcracks; the higher the degree of microcrack development, the greater the slope of the straight line of the second stage. For all of the cores, the permeability decreases as the axial pressure increases.