© 2021 Saudi Arabian Armed Forces Hospital. All rights reserved.Objectives: To examine the effects of desflurane and cerium oxide (CO) on lung tissue following ischemia-reperfusion injury (IRI). Methods: Experiments were conducted in Gazi University Animal Laboratory, Ankara, Turkey. Thirty rats were divided into 5 groups: control (C), IRI, IRI-CO, IRI-desflurane (IRID), IRI-CO-desflurane (IRICOD). Cerium oxide was given intraperitoneally. Lower extremity IRI was induced. Desflurane was applied during IRI. Lung histopathological examinations and serum biochemical analyses were performed. Results: Serum nitric oxide (NO) and malondialdehyde (MDA) levels were higher in group IRI (p=0.006) than in group C (p=0.001). Serum MDA and NO levels were significantly lower in groups IRICO and IRICOD than in group IRI. Significantly greater alveolar wall thickening and neutrophil infiltration were recorded in group IRI than in group C. Co-administration of desflurane and CO significantly decreased alveolar wall thickening and neutrophil infiltration compared to group IRI. Total lung injury scores were significantly lower in groups IRID, IRICO, and IRICOD than in group IRI. Conclusion: Intraperitoneal CO with desflurane, reduced oxidative stress and corrected the damage in lung. Cerium oxide given before and desflurane given during IRI have been shown to have protective effects on lung damage in rats.