BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is a prevalent chronic respiratory condition characterized by a complex etiology. Fibronectin 1 (FN1), an extracellular matrix protein, is known to play a significant role in inflammatory responses and tissue remodeling. This study aims to investigate the involvement of FN1 in the development and progression of COPD, providing potential insights for preventive and therapeutic strategies. METHODS: We first conducted a bioinformatics analysis to evaluate the expression of FN1 in COPD patients and then performed clinical validation. A total of 84 COPD patients and 39 healthy controls were enrolled. We measured FN1 levels in the serum and FN1 mRNA expression in the plasma of both groups. Additionally, we analyzed and compared the correlation between serum FN1 levels and lung function parameters in the healthy control group and COPD group. Next, we established a COPD model in SD rats, confirming the successful establishment of the model through HE staining. We then used immunohistochemistry and Western blot to detect the differences in FN1 expression in the lung tissues of COPD rats and normal rats. Finally, in BEAS-2B human normal bronchial epithelial cells, we overexpressed and silenced the FN1 gene to observe the effects on cell proliferation, apoptosis, and AKT phosphorylation levels. RESULTS: Bioinformatics analysis revealed that FN1 expression was higher in the COPD group compared to the normal group. ELISA and PCR analysis both showed that FN1 levels in the serum and plasma of COPD patients were significantly higher than those in the normal group (P < 0.05). Statistical analysis further revealed a positive correlation between serum FN1 levels and lung function parameters in both the healthy control and COPD groups. Western blot and immunohistochemical analysis confirmed that, in the COPD rat model, FN1 expression in lung tissues was significantly higher than in normal rat lung tissues (P < 0.05). In BEAS-2B cells, overexpression of FN1 led to increased cell proliferation, reduced apoptosis, and elevated AKT phosphorylation levels. In contrast, silencing FN1 decreased cell proliferation, increased apoptosis, and lowered AKT phosphorylation levels. CONCLUSION: Fibronectin 1 (FN1) has been implicated in the development and progression of Chronic Obstructive Pulmonary Disease (COPD). FN1 has potential as a biomarker for evaluating the prognosis of COPD patients and informing treatment strategies. Further research is essential to deepen our understanding of FN1's involvement in the pathogenesis of COPD, thereby facilitating the development of new theoretical frameworks and therapeutic interventions for managing this condition.