Abstract Background and objective: Eosinophilic chronic obstructive pulmonary disease (COPD) has been recognized as an inflammatory pattern which is importance for precise treatment interventions among COPD. However, the studies about eosinophilic COPD show conflicting results and the role of eosinophils in COPD remains unclear. In this study, LC-MS/MS-based mediator lipidomics was to determine the expression status of lipid signals in non-eosinophilic and eosinophilic COPD. Method: A totally 80 patients with COPD including 40 eosinophilic COPD and 40 non-eosinophilic COPD were enrolled over 12 months. Clinical characteristics information record, pulmonary function tests, complete blood count, serum metabolites analysis and other clinical tests were performed at baseline and follow-up. Results: There were no significant differences in pulmonary function or pulmonary function decline between eosinophilic COPD and non-eosinophilic COPD after follow-up. However, eosinophilic COPD have higher numbers of acute exacerbation patient in the last 1 year. Complete blood count (CBC) data demonstrated that Δ blood eosinophil count (BEC) was significantly decreased and correlated with Δ FEV1 (% Predicted) (r = 0.314, P = 0.036) in eosinophilic COPD. Furthermore, compared to non-eosinophilic COPD, a series of 12/15-LOX-derived mediators were found increased in eosinophilic COPD. Among them, 17-HDoHE was found significantly decreased after follow-up and significantly correlated with Δ BEC (r= 0.336, P = 0.023). Conclusion: This study demonstrates that metabolic levels of non-eosinophilic COPD and eosinophilic COPD were different due to the huge difference in eosinophil level, which leads to different inflammatory patterns, and the 12/15-LOX metabolic pathway was one of them. The results might help to understand the inflammatory response and lipid metabolism of eosinophilic COPD.