Acute lung injury is a clinical disease that causes damage to the pulmonary capillary endothelium leading to a notable ‎rate of morbidity. Clinical manifestations of SARS-CoV-2 infections vary; some persons remain asymptomatic, while ‎others develop COVID-19, with mild to critical severity. Molnupiravir is an antiviral candidate with demonstrating ‎efficacy against SARS-CoV-2. The present investigation aims at developing Molnupiravir thermosensitive in situ ‎nasal gel for the treatment of acute lung and respiratory injuries with improved therapeutic efficacy. Niosome ‎encapsulation efficiency, vesicle size, shape, and size distribution were investigated. The optimized niosomes, ‎comprised of Span® 60 and cholesterol, displayed particle size of 92.215 ± 6 nm, zeta potential of -29.67 ± 0.22 mV ‎and encapsulation efficiency of 95.36 ± 1.5%. The optimal nano-dispersion was incorporated into hydroxyethyl ‎cellulose. The resulting gels showed pseudoplastic mucoadhesive appearance with a prolonged in vitro drug release ‎pattern. Instillation of the Molnupiravir-loaded niosomal gel into rats' nasal cavity ameliorated lung damage via a ‎reduction of the cytokine storms induced by potassium dichromate (TNF-α / TGF-β). Molnupiravir-loaded niosomal ‎gel elevated PI3K/ Akt signaling pathway which promoted cellular growth. Consequently, the invented nano-‎particulate gelling system may offer an appropriate carrier for better enhancement of serious respiratory disorders‎