Abstract: Objective To investigate the protective effect of quercetin against lipopolysaccharide (LPS)- induced acute kidney injury (AKI) in mice and explore its mechanism. Methods Forty male BALB/c mice were randomly divided into control group (with saline treatment), 15 mg/kg LPS group, and quercetin-treated groups with intragastric quercetin treatment (once daily for 3 consecutive days) at low (25 mg/kg) and high (50 mg/kg) dose prior to 15 mg/kg LPS injection. LPS was administered by intraperitoneally injection 1 after the last gavage of quercetin. The mice were sacrificed 24 h after LPS injection for analysis of kidney pathologies, blood urea nitrogen (BUN) and creatinine levels; serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6 were detected by ELISA, and the expressions of Toll-like receptor-4 (TLR4), MyD88, TRAF-6 and NF-κBp65 in the kidney were detected by Western blotting. Results Quercetin significantly lessened renal pathologies, lowered BUN and creatinine levels (P<0.05) and inhibited TNF-α, IL-1β, and IL-6 production in mice with LPS-induced AKI (P< 0.05). Pretreatment with quercetin also significantly inhibited TLR4, MyD88, and TRAF-6 expressions and NF-κBp65 activation in the kidneys of the rats with LPS challenge (P<0.05). Conclusion Quercetin pretreatment can protect mice against LPSinduced AKI by inhibiting TLR4/NF-κB signaling pathway.