Abstract <p>Organophosphorus poisoning (OP), a prevalent form of pesticide intoxication, induces severe multiorgan dysfunction. While combined lipid emulsion (ILE) and standard treatment (pralidoxime methiodide &amp; atropine) demonstrate improved clinical outcomes, the therapeutic mechanisms remain elusive.</p> Methods <p>An OP rat model was established for: (1) histopathological assessment via hematoxylin-eosin (H&amp;E) staining; (2) LPS/Toll-like receptor 4 (TLR4) quantification through flow cytometry; (3) inflammatory cytokine measurement using enzyme-linked immunosorbent assay (ELISA); and (4) cytokine mRNA analysis via reverse transcription PCR (RT-PCR). TLR4 pathway validation employed anti-TLR4 intervention.</p> Results <p>After survived 24&#xa0;h, multiple organs were damaged in rats with organophosphorus poisoning. Treatment with standard treatment or only lipid emulsion slightly alleviated the symptoms of poisoning, However, when standard treatment was combined with lipid emulsion, the symptoms were significantly alleviated, and the expression level of TLR4 was significantly decreased in the ST + ILE group. After anti-TLR4 was used to block the LPS/TLR4 pathway, liver function and acetylcholinesterase(AchE) levels in rats were significantly improved(<i>P</i> &lt; 0.001), lung and heart pathology improved, and inflammatory cytokines were reduced; Moreover, the expression level of TLR4 in heart and lung also decreased significantly(<i>P</i> &lt; 0.01). As a result, the symptoms of organ poisoning were relieved.</p> Conclusion <p>Lipid emulsion is involved in the protective effect via the LPS/TLR4 pathway on vital organs inacute or organophosphorus poisoning.</p>