Background: Acute respiratory distress syndrome (ARDS), a clinical syndrome resulting from intrapulmonary and/or extrapulmonary causes, is characterized by refractory hypoxemia. Currently, venovenous extracorporeal membrane oxygenation (VV ECMO) is considered as a reasonable alternative to salvage ARDS, but it requires sedation of the patient. Several studies suggest that anesthetics, such as sevoflurane and propofol, have lung protective and immunomodulatory functions. The aim of this study was to explore the effects of sevoflurane and propofol on ARDS in VV ECMO rat models.Methods: To establish the ARDS model, male Sprague-Dawley (SD) rats were injected with 100mg/kg oleic acid (OA). Twenty-four SD rats were randomly divided into two groups: sevoflurane group (Sevo group) and propofol group (Pro group). The basic vital signs of rats in each group were continuously monitored using a life monitor, and arterial blood gas tests were performed at the following three time points: T0 (baseline), T1 (the time to ARDS), and T2 (after weaning from ECMO for 1 h). Bicinchoninic acid assay (BCA) method was used to determine protein concentration in bronchial alveolar lavage fluid (BALF), whereas hemotaxylin and eosin (HE) staining was used to evaluate the lung pathological scores in each group. In addition, inflammatory factors (IL-1b, TNF-a, and MPO) in BALF, serum, and lung were determined using enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC).Results: With regard to the blood gas index, the Sevo group exhibited a better effect in improving the oxygenation function than the Pro group (P<0.05). However, there was no significant difference in mean arterial pressure (MAP) between the two groups (P>0.05). After VV ECMO assistance, the degree of lung injury and inflammatory changes in the Sevo group were significantly reduced compared to the Pro group.Conclusion: This study shows that sedation with sevoflurane during VV ECMO assisted ARDS in rats improved lung injury and inflammation, and was better than propofol in improving the oxygenation function.