Abstract It has long been recognized that the solid particles in circulating fluidized bed risers are distributed heterogeneously in the form of clusters. In response to this fundamental phenomenon, an EMMS-based two-fluid model has been developed recently from the viewpoint of continuum mechanics, however, its microscopic foundation remains unknown. In this study, the statistical mechanics foundation of EMMS-based two-fluid model was presented using generalized Boltzmann kinetic theory. With respect to the gas phase, a new method was developed by considering the fluctuations at different scales simultaneously, with which we can for the first time derive the correct governing equations of gas phase via kinetic theory, in the sense that both the molecular stress and the Reynolds (or pseudo-Reynolds) stress can be obtained simultaneously, whereas all previous kinetic theory analyses failed to predict the appearance of Reynolds (or pseudo-Reynolds) stress in the momentum conservation equation of gas phase due to the assumption of uniform structure, although it is physically always existent no matter how small the Reynolds number is. In case of particle phase, the generalized Boltzmann equation considering the spatio-temporal variation of the volume, density and velocity of clusters was firstly derived, a set of macroscopic transport equations was then derived in different phase spaces. It was shown that the governing equations of dense phase in the EMMS-based two-fluid model derived from continuum mechanics viewpoint corresponds to the macroscopic transport equations at ( r , t ) space. Therefore, present study launches a solid microscopic foundation of EMMS-based two-fluid model. Finally, CFD simulations have been carried out to validate EMMS-based two-fluid model and to study the effect of gas phase pseudo-turbulence.