In the underground repositories, the microstructure change of surrounding rock mass under the chemical reaction will cause the porosity change in medium. Aiming at the chemical reaction effect on the environment medium, the porosity of sandstone specimens, along with Ca2+ concentration of solution were tested. Based on the analysis of test results and the theory of chemical thermodynamics, the chemical action mechanism was concluded for absorption of Ca2+. With the combination of the theories of chemical kinetics, chemical thermodynamics, and solute transportation, a reactive-transport model to describe porosity change under chemical reaction was established. Finally a simplified chemical model was advised to describe microstructure change of rock under chemical reaction. And the numerical simulation analysis was performed. The simulation result indicates that with the reaction time increasing, the porosity reduces firstly and then is driven to stabilization in the end. The study results can be used as a valuable reference to understand the mechanism of the chemical reaction effect on the microstructure change of sand rock.