Abstract: In order to explore the protective effect and related mechanism of chlorogenic acid（CGA） on sepsis-induced acute kidney injury（AKI） in rats, thirty-two healthy male SD rats were selected and randomly divided into 4 groups, namely control group（CON group）, model group（LPS group）, CGA intervention group（CGA + LPS group） and CGA group. The rats in the LPS group were intraperitoneally injected with 10 mg/kg LPS according to their body weight to establish a rat model of sepsis; the rats in the CGA + LPS group were intraperitoneally injected with 20 mg/kg CGA according to their body weight, and LPS was injected intraperitoneally 1 hour later; the CGA group was intraperitoneally injected wih 20 mg/kg CGA according to their body weight. After 4 h, the rats were anesthetized with isoflurane; the abdominal cavity was opened; urine was collected from the bladder and blood was collected from the heart for the detection of renal function and serum inflammatory factors respectively. H.E. staining was used to observe the histopathological changes of the kidney. Western-blot method was used to detect the relative expression of nuclear factor E2 related factor 2（N-Nrf2）, total（T）-Nrf2, Heme oxygenase 1（HO-1）, NAD（P）H quinone oxidoreductase 1（NQO1） proteins and NLR family pyrin domain containing 3（NLRP3） inflammasome-related proteins（NLRP3, Caspase1 p20, IL-1β and IL-18） in renal tissue. The results showed that compared with the CON group, the serum urea nitrogen（BUN） and creatinine（Cre） levels in the LPS group were significantly increased（P＜0.01）; the urinary KIM-1 and NGAL levels were extremely significantly increased（P＜0.01）; the serum inflammatory cytokine levels of TNF-α, IL-6, IL-1β and IL-18 were significantly increased（P＜0.01）; renal histopathological changes included renal tubular dilatation or swelling, vacuolar degeneration, and inflammatory cell infiltration; the relative expression levels of NLRP3 inflammasome-related proteins（NLRP3, Caspase1 p20, IL-1β and IL-18） were significantly increased（P＜0.01）, while the relative expression levels of Nrf2, HO-1 and NQO1 proteins were not significantly different（P＞0.05）. Compared with the LPS group, the serum BUN and Cre levels of the CGA + LPS group were significantly decreased（P＜0.01）; the urinary KIM-1 and NGAL levels were extremely significantly decreased（P＜0.01）; the serum inflammatory cytokine levels of TNF-α, IL-6. The of IL-1β and IL-18 were significantly decreased（P＜0.01）; only mild inflammatory cell infiltration and focal necrosis were seen in renal histopathological changes; Nrf2, HO-1 and NQO1 protein expressions were extremely significantly increased（P＜0.01）; the expression of NLRP3 inflammasome-related proteins（NLRP3, Caspase1 p20, IL-1β and IL-18） was extremely significantly decreased（P＜0.01）. The results suggested that CGA promoted the expression of downstream HO-1 and NQO1 proteins by activating the Nrf2 signaling pathway, inhibited the activation of NLRP3 inflammasome, and alleviated the inflammatory cascade reaction, thereby protecting the LPS-induced rat AKI.