A network model for CS-induced immune response in COPD progression in this work is developed based on established literature knowledge. Upon exposure to CS, immature alveolar macrophages (M0) are classically activated directly by the CS particulate phase  and polarized to the inflammatory phenotype (M1) in the lung [20, 21]. The M1 cells produce inflammatory cytokines such as TNF-α, which activates M1 conversely, IL-6 and IL-12 [22, 23]. M1 can cause tissue damage (TD) in the lung by releasing reactive oxygen species (ROS) leading to oxidative stress, proteases such as macrophage elastase and metalloproteases (MMPs) to ingest pathogens and apoptotic cells, and chemokines to recruit neutrophils into the lung [24–26]. Neutrophils, which are short-lived and subsequently cleared by macrophages , can also cause TD in a manner similar to macrophage . Furthermore, the tissues damaged by M1 can produce elastin fragments (EFs) as strong attractors to recruit monocytes (precursors of macrophages, M0) into the lung from circulation .Subsequently, these M0 cells are differentiated into M1, thus forming a positive feedback loop, M1→TD→M1. In addition, TD can also be caused directly by CS .