The pathogenesis of endotoxin-induced acute lung injury is fundamentally driven by dysregulated innate immune responses, where macrophage-mediated cytokine surges and subsequent signaling cascades trigger neutrophil infiltration and tissue damage.This study investigated whether curcumin modulates inflammatory signaling pathways and attenuates lung injury in experimental endotoxemia. Using endotoxin-stimulated murine macrophages and a mouse model of intratracheal lipopolysaccharide challenge, inflammatory cytokine production, mitogen-activated protein kinase activation, pulmonary edema, neutrophil accumulation, histopathologic injury, and short-term survival were assessed. Curcumin suppressed endotoxin-induced tumor necrosis factor- production and selectively inhibited ERK1/2 and JNK phosphorylation without affecting p38 signaling in macrophages. In vivo, curcumin reduced pulmonary cytokine levels, neutrophil infiltration, lung edema, and histologic injury, and was associated with improved survival following severe endotoxin exposure. These findings indicate that curcumin attenuates acute lung injury by selectively modulating intracellular inflammatory signaling pathways, supporting the concept that targeted inhibition of specific kinase cascades may mitigate inflammatory lung damage without broad immune suppression.