A new method of calculating the grand partition function of many-body system is developed, adopting extensively the techniques of calculus in quantum field theory. It is shown that the grand partition function, which is a trace of the density matrix expressed in terms of field operators, can be evaluated in a way almost parallel with the evaluation of the vacuum expectation value of the S-matrix in quantum field theory, provided that appropriate modifications in notation and definitions are made. As an example, the method is applied to electron-phonon system. Further, basing on this new formalism, various non-perturbational methods are discussed.