Compacted bentonite–sand mixture (CBM) is a kind of candidate buffer material of high-level radioactive waste (HLW) disposal in many countries. It is believed that the permeability of CBM is greatly related to its microstructure. The aim of this study was to search the effect of various aqueous mediums on the microstructure and pore characteristics of this buffer material. Permeation experiments and X-ray computerized tomography (X-ray CT) were used to explain the correlation between microstructure and permeability. Representative samples of CBM at a dry density of 1.7 g/cm3 were used. X-ray CT was used to study the CBM under the de-ionized water (DI) and three other aqueous medium conditions. After reconstruction with Dragonfly software, the pore characteristics and permeability of different solution-saturated samples were analyzed using AVIZO software, including pore size distribution (PSD), porosity, and connectivity. The results showed that the permeability coefficient of samples was NaOH > NaCl-Na2SO4 > Simulated Beishan groundwater > DI water, and the maximum swelling pressure of samples was NaOH < NaCl-Na2SO4 < Simulated Beishan groundwater < DI water. The permeability coefficient decreased with the increasing of maximum swelling pressure. Quantitative analysis indicated that the volume of interconnected pores increased owing to the infiltration of NaCl-Na2SO4 and NaOH.