This paper describes a separation model in capillary electrophoresis (CE) based on the entropy equation of nonequilibrium thermodynamics. We first related AS, the mixed entropy change of the solute system, to plate height (H) and △S, the contribution of △S only due to the net separation process, to resolution (Rs) and resolution product (I1R~). In particular, we determined the entropy flow of the solute system, which is composed of both energetic and material exchange terms relating to capillary cooling and relative migrations among solute zones, respectively. It is just the CE separation system, as exterior surroundings, that contributes to the enhanced separation efficiency. The more the CE system (except the solute system) provides the solute system with negative entropy flow, the better the separation efficiency of the CE system. We also determined six thermodynamic forces and their thermodynamic fluxes corresponding to six irreversible processes; heat conduction, four kinds of diffusion (electrical field, axial concentration gradient, electrophoretic dispersion and wall adsorption) and viscous flow, respectively. Entropy production is thus composed of the six terms corresponding to time-dependent CE efficiency loss factors. The bigger the entropy production, the greater the loss of separation efficiency. The objective functions were built based on the entropy equation of solute systems developed between CE separation efficiency (ASS) and the optimizing parameters (electrical strength, coolant temperature; the composition and concentration of buffer; the radius, length and wall adsorption of the capillary; the concentration, charge, molecular weight and conformation of solutes; injection conditions, etc.). The more negative △SS is, the better the separation efficiency. This model was supported by the results of our experiments and data in the literature.