Severe influenza is characterized by damage and morphofunctional changes of the endothelium of blood vessels, which contributes to the development of hemorrhagic syndrome and can cause endothelial dysfunction. To optimize the pathogenetic therapy of influenza infection, a screening of medications with endothelial protective properties was carried out.The aim of the study was to evaluate the endothelial protective properties of sacubitril/valsartan and drotaverine in influenza A(H1N1)pdm09 virus infection.The study was conducted on Wistar rats, which received sacubitril/valsartan and drotaverine (in treatment and prophylactic regimen) followed by intransal infection with influenza A/Saint-Petersburg/48/16 (H1N1)pdm09 virus. Rats without drug administration were included in the control group; rats received no medications followed by influenza virus infection - in challenge control group. The virus infectious activity was determined in pulmonary and mesenteric tissues. Vascular endothelium damage in lungs was assessed by three parameters (desquamation, morphological and dystrophic changes). Endothelial nitric oxide synthase (eNOS) expression level in endothelium of mesenteric blood vessels was determined as well as mesenteric arteries vasomotor activity.Drotaverine reduces the severity of histopathological changes in the pulmonary vascular endothelium; increases the maximal response of mesenteric blood vessels to acetylcholine compared to the infection control group; normalizes eNOS expression levels. Sacubitril/valsartan reduces the severity of desquamation in the pulmonary vascular endothelium; normalizes the response of mesenteric blood vessels to acetylcholine, while eNOS expression is decreased.Drotaverine possesses more significant endothelial protective properties than sacubitril/valsartan when used in a treatment and prophylactic regimen in rats infected with influenza A(H1N1)pdm09 virus.