This study mainly explored the effect of Tempol on OSA-induced lung injury and the specific molecular mechanism. A hypoxia/reoxygenation (H/R) cell model and an IH-induced lung injury model in rats were constructed. The expression of miRNAs and related proteins was detected by RT‒qPCR and Western blotting. HE and Masson staining were used to observe the pathological changes in lung tissues. The expression levels of inflammatory cytokines were detected by ELISA. Apoptotic cells were observed by TUNEL. The ROS levels were detected by a DCFH-DA probe. Tempol administration effectively reduced the pathological changes in lung tissue and the progression of pulmonary fibrosis in rats with lung injury and reduced the expression of inflammatory factors in lung tissue. miR-145-5p was significantly upregulated in rats with IH-induced lung injury, and Tempol treatment inhibited the expression of miR-145-5p. Transfection with the miR-145-5p inhibitor effectively inhibited H/R cell apoptosis and autophagy, while transfection with the miR-145-5p mimic had the opposite effect. Targeting miR-145-5p negatively regulates the expression of Nrf2. Transfection of the miR-145-5p mimic weakened the inhibitory effects of Tempol on apoptosis and autophagy in H/R cells. Overexpression of the Nrf2 mimic reversed the effects of the miR-145-5p mimic on Tempol to a certain extent. It was also confirmed in animal experiments that overexpression of Nrf2 reversed the inhibitory effect of the miR-145-5p mimic on Tempol's lung injury relief effect. Tempol alleviates lung injury induced by chronic interstitial hypoxia by regulating the miR-145-5p/Nrf2 molecular axis and inhibiting autophagy.