Few years ago, we have succeeded to “probe” water molecules bound in a cavity of a protein by means of the statistical mechanics of molecular liquids, or the RISM/3D-RISM theory. This is the first finding in the history of the statistical mechanics to show that the theory is applicable to such fluids in an extremely inhomogeneous field in atomic scale. On the other hand, the finding implies that we got a powerful machinery in our hand to clarify the “molecular recognition” which is the most fundamental process in living cells. It will become a “bridgehead” in our theoretical challenge on life phenomena. In the succeeding applications of the method, we have focused on a variety of molecular processes in bio-systems, in which the molecular recognition plays an essential role: the selective ion-binding by protein, an enzymatic reaction, water channels (aquaporin), the preferential binding of inert gas by protein, and the pressure denaturation of protein. In the talk, I will present our recent studies on the chemical processes concerned with the molecular recognition, focusing especially on the possibility of ion permeation through aquaporins. The talk will include also prospects of the theory to be extended to the temporal fluctuation of protein structure coupled with the solvent dynamics.