The aim of the study is to examine structural and ultrastructural aero-hematic barrier (AHB) changes in rats during adaptation to high-altitude hypoxia. Materials and Methods. The experiments were carried out on 60 sexually mature outbred laboratory male rats weighing 140–160 g at high altitude (3200 m above sea level). The authors followed Mayer's hematoxylin and eosin staining protocol, and used transmission and scanning electron microscopy on the 7th, 15th and 30th days of the animals' life in the mountains. Statistical data processing was carried out using Statistica 6.0 (USA) and StatTech v. 2.8.4 (Russia) and Student's t-test. Differences were considered statistically significant at p<0.05. Results. At early stages of high-altitude adaptation, dystrophic changes in the epithelial layer of lung capillaries, hypertrophy and hyperplasia of histiocytes, fibroblasts and lipofibroblasts were noted. The authors also revealed proliferation of type II alveolocytes, thickening of the interalveolar septa (IAS) and cytoplasmic processes of endotheliocytes, destruction of type II alveolocytes (apocrine method, with the release of surfactant into the alveoli lumen), multivesicular lamellar bodies in the cytoplasm of type II alveolocytes; interstitial edema with transudate in the alveoli lumen. In later periods, surfactant system activity decreases due to a reduced release of osmiophilic lamellated corpuscles (OLC) into the alveoli lumen. The main AHB components are next to control data, while the IAS thickness exceeds the norm. In the alveoli wall, the number of fibroblasts increases, causing an increase in the number of Kohn's pores and providing collateral breathing. Conclusion. The study of AHD components in experimental animals at different periods of high-altitude adaptation revealed dystrophic processes of AHD in IAS, compensated by type I alveolocytes and proliferation of type II alveolocytes, confirming the adaptive mechanisms of ultrastructural alteration of all epithelial and endothelial components of the pulmonary alveoli.