Acute lung inflammation is characterized by critical tissue hypoxia, a massive inflammatory cascade, and microvascular thrombosis, which leads to high mortality and pulmonary fibrosis, especially in severe viral infections, including COVID-19. Key regulators of the cellular response to hy- poxia are hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF), excessive activation of which leads to pathological angiogenesis, increased vascular permeability, and the formation of pulmonary fibrosis. The effectiveness of experimental therapies aimed at blocking angiotensin-converting enzyme 2 (ACE2) receptors, sup- pressing the inflammatory response with glucocorticoids, and preventing microthrombosis with the anticoagulant heparin was evaluated based on their effect on HIF-1α and VEGF content in lung tissue. Acute lung inflammation was modeled in male Wistar rats weighing 190-220 g (n = 45). From days 5 to 21, the rats were administered drugs by inhalation. After this, a histological examination of the lung tissue was per- formed, along with an immunoblotting analysis to determine the content of HIF-1α and VEGF. It was found that the use of the ACE2 blocker camostat mesylate, methylprednisolone, and enoxaparin sodium reduced the content of HIF-1α in the lungs compared to placebo. The dynamics of the monomeric form of VEGF corresponded to changes in HIF-1α but decreased less pronouncedly. Morphologically, the HIF-1α/VEGF inhibition corresponded to the fibrosis reduction. The drugs used demon- strated different effects: the maximum effect on HIF-1α was observed with camostat mesylate, on the VEGF monomer was enoxaparin sodium, and on fibrosis was methylprednisolone. The revealed correlation between the reduction in tissue HIF- 1α/VEGF content and the reduction in inflammatory damage and fibrosis substantiated the feasibility of further developing these therapeutic approaches to prevent pulmonary inflamma - tory complications.