BACKGROUND: Baclofen is a selective agonist of γ-aminobutyric acid B receptors. The drug exhibits pronounced psychotropic effects and frequently causes dependence. However, its impact on the cardiovascular and respiratory systems remains underexplored. AIM: To evaluate the dynamics of specific functional parameters of the cardiovascular and respiratory systems, as well as histological changes in the lungs, in cases of baclofen poisoning and its combination with ethanol. MATERIALS AND METHODS: Baclofen and its combination with ethanol were administered to rats under general anesthesia (chloral hydrate 300 mg/kg, intramuscularly). Animals in the control group (n=5) Submitted no baclofen or ethanol. Animals in Groups 1, 3, and 5 were administered baclofen at a dose of 85 mg/kg, with physiological parameters recorded at 3, 4.5, and 24 hours. Animals in Groups 2, 4, and 6 were administered baclofen at the same dose combined with 40% ethanol (7 ml/kg). Physiological parameters (oxygenation level, red blood cell count per liter of blood, and hemoglobin concentration in g/L) were recorded at the same time points. The animals were then euthanized by cervical dislocation under general anesthesia (chloral hydrate), and biological material was collected for subsequent studies. Morphometric analysis was performed using G.G. Avtandilov’s grid. RESULTS: Baclofen and its combination with ethanol led to a statistically significant decrease in oxygenation levels. Red blood cell count and hemoglobin concentration (g/L) remained unchanged. A dynamic complex of pathological changes developed in the lungs of experimental animals, including microcirculation disturbances, thickening of interalveolar septa due to edema, and leukocyte infiltration. Three hours after combined administration of baclofen and ethanol, a statistically significant increase in vessel area was observed. At 4.5 hours, the areas occupied by leukocytes, the ratio of leukocyte area to interalveolar septa area, and the area affected by edema increased significantly. After 24 hours, the leukocyte area, the ratio of leukocyte area to interalveolar septa area, and the edema area further increased. CONCLUSION: Combined with chemical-toxicological findings, the data obtained from this study allow for the identification of baclofen poisoning, estimation of the time elapsed since poisoning, and assessment of exposure conditions. Understanding the processes occurring in the lungs following baclofen and ethanol administration may enhance the effectiveness of medical assistance for affected individuals. © Eco-Vector, 2024.