Circulating fluidized bed (CFB) systems are the core unit of many chemical and energy processes. Realizing a full-loop CFB system simulation can help one understand system operation laws for achieving optimal production. This study realizes a full-loop simulation of a 1.20 Mt/a industrial reaction− regeneration CFB system by applying mesoscale drag and constructing a mechanical valve pressure regulation model. The effects of the energyminimization multiscale (EMMS)-based drag models are investigated by analyzing the solid concentration, full-loop pressure balance, and mass flow rate. Then, the flow characteristics of the single-riser and full-loop simulations are compared. It is found that the single-riser simulation predicts a wider frequency distribution of solid concentration (average value ≈1.6 Hz), while the full-loop simulation captures a dominating frequency at a much lower value (≈0.1 Hz), indicating that the above two kinds of simulations reveal significantly different mechanisms in particle conveying and dynamic behavior of mesoscale structures.