Unlike the conventional drag models which were developed on the basis of experiments with homogeneous system, energy minimization multi-scale (EMMS) drag model takes into account the heterogeneous structure inside the gas-solid flow. In this paper, the transient three-dimensional full-loop gas-solid flow in a pilot scale circulating fluidized bed (CFB) with six cyclones was simulated in the computational particle fluid dynamics (CPFD) method, based on EMMS. Particle volume fraction distribution, time averaged pressure profile, and averaged particle vertical velocity were analyzed and presented. The results show that under the simulation condition, in the dense region, particles agglomerate and form clusters; pressure drop evaluation of the dense region is still far away from the experimental data but better than using Wen-Yu model; vertical velocity profile shows core-annulus structure.