Abstract： Background Leptin is a protein mainly secreted by adipocytes, and the major function of leptin was its role in body weight regulation. It is suggested that increased levels of circulating leptin may contribute to anorexia in pathologic conditions including chronic obstructive pulmonary disease (COPD). Recent studies have provided evidence for a link between leptin and proinflammatory cytokines such as tumor necrosis factor-α (TNF-α). This study aimed to explore the role of serum leptin in the malnutrition of COPD patients, and to observe the changes of serum leptin levels during acute exacerbation, also to investigate relationship between leptin and TNF-α. Methods Seventy-two COPD patients and 34 control subjects participated in this study. Seventy-two COPD patients were divided into 3 groups: group COPD IA (patients without malnutrition during acute exacerbation, n=25), group COPD IB (patients without malnutrition during stable disease, n=29), group COPD II (patients with malnutrition during stable disease, n=18). To eliminate the effect of sex differences, all patients and controls were male. Body mass index (BMI), percent ideal body weight (IBW%), triceps skin-fold thickness (TSF), mid-upper arm circumference (MAC), mid-upper arm muscle circumference (MAMC), serum leptin and TNF-α levels, serum prealbumin (PA), serum transferrin (TF), serum albumin (Alb), total lymphocytes count (TLC), forced expiratory volume in one second (FEV1), maximal inspiration pressure (MIP) and maximal expiration pressure (MEP) were measured in all participants. Leptin levels were measured by radioimmunoassay. TNF-α levels were measured by ELISA. The between group difference and correlation of these parameters were analyzed. Results Serum leptin levels were significantly lower in group COPD II [(4.07±3.42) ng/ml] than in group COPD IB [(9.72±6.67) ng/ml] and controls [(8.21±5.41) ng/ml] (P<0.05). There was no statistically significant difference in serum leptin levels between group COPD IA [(10.82±6.40) ng/ml], group COPD IB [(9.72±6.67) ng/ml] and controls [(8.21±5.41) ng/ml]. There was no statistically significant difference in serum TNF-α levels between group COPD II [(8.03±3.37) pg/ml], group COPD IA [(8.90±1.60) pg/ml], and group COPD IB [(7.25±2.08) pg/ml]. There was no significant correlation between leptin and TNF-α in any group. Conclusions Leptin was not involved in anorexia and weight loss of COPD patients. There was no statistically significant difference in serum leptin levels between COPD patients during stable stage and acute exacerbation, and there was no significant correlation between TNF-α and leptin during the regulation of the energy balance in COPD patients.