Hesperetin, a major bioflavonoid in sweet oranges and lemons, exerts an anti-inflammatory effect in pulmonary diseases; however, its effect on lipopolysaccharide (LPS)-induced acute lung injury is unclear. This study investigated the effect of hesperetin on LPS-induced lung inflammatory response. Mice were intratracheally instilled with 5 mg/kg body weight LPS, and then were given hesperetin orally (10, 20, and 30 mg/kg body weight) 1 h later. Hesperetin dramatically suppressed the levels of interleukin-6 and tumor necrosis factor-α, as well as the number of inflammatory cells in bronchoalveolar lavage fluid. Besides, it reduced lung injury, wet weight/dry weight ratio, and myeloperoxidase and lactate dehydrogenase activities, and enhanced superoxide dismutase activity. In addition, hesperetin significantly downregulated the Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88) protein expression and suppressed nuclear factor-kappa B (NF-κB) activation in lung tissue. Together, these results indicated that the anti-inflammatory effect of hesperetin is associated with the TLR4-MyD88-NF-κB pathway, and that hesperetin shows therapeutic potential for LPS-induced acute lung injury VSports手机版. .