Streptochlorin, a tiny chemical produced from a marine actinomycete, possesses anti-angiogenic, anti-tumor, and anti-allergic properties. The anti-inflammatory effects and underlying mechanisms, however, have yet to be discovered. The effect of streptochlorin on Lipopolysaccharide (LPS)-induced inflammatory reactions in vitro and in vivo was examined in this work. Streptochlorin inhibited the Toll/Interleukin-1 receptor (TIR)-domain-containing adaptor, which reduced the generation of proinflammatory mediators such as nitric oxide, cyclooxygenase-2, pro-interleukin (IL)-1, and IL-6 in LPS-stimulated RAW264.7 cells. TRIF-dependent signalling mechanism that induces interferon In the LPS-induced Acute Lung Injury (ALI) animal model, streptochlorin inhibited the infiltration of immune cells such as neutrophils into the lung and the generation of proinflammatory cytokines such as IL-6 and TNF- in Broncho-Alveolar Lavage Fluid (BALF). Streptochlorin exhibits powerful anti-inflammatory effects by modulating TRIF-dependent signalling pathways, suggesting that it could be a useful therapeutic method for a variety of inflammatory illnesses.