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Yingqi Wang,1,* Yidie Bao,1,* Boya Liu,1,* Hui Li,1 Hongxia Duan,1 Yide Wang,2 Jiachi Zhang,1 Weibing Wu,3 Peijun Li,1 Xiaodan Liu1 1School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Department of Rehabilitation, The Fourth Clinical Medical College of Xinjiang Medical University, Urumqi, People’s Republic of China; 3School of Exercise and Health, Shanghai University of Sport, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaodan Liu, School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Cailun Road No. 1200, Pudong New Distinct, Shanghai, 201203, People’s Republic of China, Email hzhp403@126.com Peijun Li, School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Cailun Road No. 1200, Pudong New Distinct, Shanghai, 201203, People’s Republic of China, Email lpj0227@163.comAbstract: Chronic obstructive pulmonary disease (COPD) ranks among the leading causes of global mortality, with chronic inflammation as its primary pathogenic mechanism. Developing effective therapeutic strategies to attenuate this inflammatory response is crucial for reducing the prevalence, mortality, and overall burden of COPD. Polyunsaturated fatty acids (PUFAs) are recognized for their role in modulating inflammation and may influence inflammation-driven diseases. This narrative review evaluates observational and interventional studies on PUFAs in COPD and explores their potential mechanisms in modulating inflammation. The synthesis of the literature reveals limited and inconsistent evidence linking PUFAs to COPD. Robust data are lacking to conclusively demonstrate the biological benefits and clinical efficacy of n-3 PUFAs in COPD. Therefore, we systematically assess current research and recommends extensive and rigorous future clinical trials. Furthermore, PUFAs and their derivatives play roles in initiating and resolving inflammation in COPD through direct involvement, macrophage polarization regulation, and effects on membrane biophysics and signal transduction. Despite the current inconclusive evidence, we emphasize the necessity for intensified clinical trials and drug development efforts targeting PUFAs in COPD to develop new therapeutic strategies.Keywords: n-3 PUFAs, n-6 PUFAs, COPD, inflammation, specialized pro-resolving lipid mediators, eicosanoid