Objective: To observe and study the changes of lung function and serum cytokine levels in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and their correlation with smoking and body mass index (BMI). Methods: A total of 102 patients with AECOPD who were treated in our hospital from June 2020 to December 2020 were selected as the research objects; 50 patients who smoked were included in the smoking group, and 52 patients who had quit or had no smoking history were included in the non-smoking group; at the same time, 50 healthy volunteers who underwent physical examinations in the hospital at the same time were selected into the control group. The forced expiratory volume in one second (FEV1) and the percentage of carbon monoxide diffusion to the predicted value (DLco%) of the three groups of subjects were determined and compared; and the expression of serum cytokines such as procalcitonin (PCT), high-sensitivity C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were collected in three groups at the same time, and the correlation between lung function and serum cytokine levels, smoking index (SI) and BMI were analyzed. Results: The FEV1 and DLco% of AECOPD patients in the smoking group were significantly lower than those in the non-smoking group and the control group, and the difference was statistically significant (P<0.05). From the perspective of serum cytokine expression, the serum expression levels of PCT, CRP, IL-6 and TNF-α in AECOPD patients in the smoking group were significantly higher than those in the non-smoking group and the control group, and the difference was statistically significant (P<0.05). The FEV1 and DLco% of high-SI patients were significantly lower than those of low-SI patients, and the difference was statistically significant (P<0.05). In terms of serum cytokine expression, the serum expression levels of PCT, CRP, IL-6 and TNF-α in patients with high SI were significantly higher than those in patients with low SI, and the difference was statistically significant (P<0.05). The SI of AECOPD patients was significantly positively correlated with PCT, CRP, IL-6 and TNF-α (P<0.05), and was significantly negatively correlated with lung function (P<0.05); and the BMI of AECOPD patients was significantly positively correlated with PCT, IL-6 and TNF-α (P<0.05), but not significantly correlated with lung function (P>0.05). Conclusion: AECOPD patients with long-term smoking history have significantly higher expression levels of serum cytokines such as PCT, CRP, IL-6 and TNF-α, while their lung function status is significantly worse. The smoking status and body mass status of AECOPD patients are important indicators to measure the expression of inflammatory factors in the patient’s body, and have obvious correlation with the changes of patients’ serum cytokines. More attention should be paid to smoking patients with high BMI.