Chronic rhinosinusitis with eosinophilia (ECRS) is a refractory sinusitis characterized by eosinophilia in the nasal mucosa and peripheral blood. In ECRS, multiple nasal polyps are present in the ethmoid sinuses, and the disease is often accompanied by olfactory dysfunction and asthma. It is a disease that significantly impairs the quality of life of patients by causing persistent nasal congestion and thick nasal discharge, leading to decreased concentration and insomnia. From previous studies, we found that (1) defects in Cu,Zn-SOD in ECRS epithelium contribute to increased IL-17A, macrophage infiltration in the subepithelial tissue, and excessive production of mucin gene (MUC5AC) in the epithelium, thereby potentially exacerbating inflammation and excessive mucus secretion, and (2) reduced HO-1 expression in the epithelium and macrophage infiltration are associated with epithelial damage in CRS accompanied by eosinophil infiltration. These findings suggest that antioxidants may play a crucial role in elucidating the pathophysiology of refractory diseases such as ECRS and may provide new therapeutic strategies. In this paper, three new comprehensive molecular signaling pathway networks of (1) oxidative stress, (2) inflammation inhibition mechanisms and (3) inflammation in ECRS were developed for the first time, based on a critical analysis of scientific literature. In addition, three immunology flowsheets related to oxidative stress, inflammation and carbon monoxide-based inflammation inhibition mechanisms of ECRS were developed for the first time and examined from both clinical and biochemical perspectives. Based on these pathways, this study identified the treatment targets which can be used in future ECRS treatments.