The permeability of tight shale formations varies from micro-Darcy to nano-Darcy. Recently, hydrogen peroxide (H2O2) was tested as an oxidizer to remove the organic matter in the rock in order to increase shale permeability. In this study, shale particles were reacted with hydrogen peroxide solutions under different temperature and pressure conditions in order to “mimic” underground geology conditions. Then, low-temperature nitrogen adsorption and desorption experiments were conducted to measure the pore diameters and porosity of raw and treated shale samples. Moreover, scanning electron microscopy (SEM) images of the samples were analyzed to observe pore structure changes on the surface of shale samples. From the experiments, it was found that the organic matter, including extractable and solid organic matter, could react with H2O2 under high temperature and pressure conditions. The original blocked pores and pore throats were reopened after removing organic matter. With the increase of reaction temperature and pressure, the mean pore diameters of the shale samples decreased first and then increased afterwards. However, the volume and Brunauer–Emmett–Teller (BET) surface areas of the shale particles kept increasing with increasing reaction temperature and pressure. In addition to the effect of reaction temperature and pressure, the pore diameter increased significantly with the increasing reaction duration. As a result, H2O2 could be used to improve the shale permeability.