ObjectiveTo investigate the dynamic changes of plasma fractalkine (FKN) and Claudin-5 levels in patients with acute respiratory distress syndrome (ARDS) and their clinical significance. MethodsIn this prospective observational study, 36 ARDS patients and 20 healthy controls admitted to the ICU of the General Hospital of Ningxia Medical University from January 2022 to December 2024 were enrolled. Plasma FKN and Claudin-5 levels were measured on days 1, 3, and 5, and their relationships with disease severity and patient outcomes were analyzed. ResultsCompared with the control group, plasma FKN levels in ARDS patients were significantly elevated on days 1, 3, and 5 ( P<0.01), while Claudin-5 levels were significantly decreased on days 1 and 3 (P<0.05), with no significant difference on day 5 (P>0.05). On days 1 and 3, patients with severe ARDS exhibited significantly higher FKN levels and lower Claudin-5 levels than those with mild-to-moderate ARDS (P<0.05). Prognostic analysis showed that, on day 5, plasma FKN levels were significantly lower in the survival group than in the death group,whereas Claudin-5 levels were significantly higher (P<0.01). Correlation analysis demonstrated that FKN levels were positively correlated with Murray lung injury score (r=0.583, P<0.01) and negatively correlated with oxygenation index (r=?0.350, P=0.04). In contrast, Claudin-5 levels were negatively correlated only with Murray score (r=?0.453, P<0.01). ConclusionFKN and Claudin-5 exhibit dynamic changes during the course of ARDS. Their levels are associated with disease severity and prognosis and may serve as potential biomarkers reflecting inflammatory response and pulmonary barrier injury, with potential value in clinical assessment.