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Objective To investigate the effect and mechanism of celastrol on lipopolysaccharide（LPS）-induced acute lung injury（ALI）in septic rats. Methods Eighteen male SD rats were randomly divided into the control group， model group，and celastrol group with 6 rats in each group. The rats in the model group were injected with 5 mg/kg LPS through tail vein to establish ALI models. The rats in the celastrol group were injected with the same amount of LPS through tail vein and 1 mg/kg of 0. 02% celastrol intraperitoneally. The rats in the control group were separately injected with the same amount of normal saline through tail vein and abdominal cavity. After 24-hour culture，the abdominal aorta blood was collected，and PO2 of the abdominal aorta was detected by blood gas analyzer. Rats were executed with narcotic overdose，and the chests in the rats were dissected under aseptic conditions. The left lung tissues were taken，and the wet weight was weighed. After drying in the oven，the dry weight of rats was weighed，and the ratio of the wet weight to the dry weight of the lung tissues（W/D）was calculated. The inferior lobe of right lung in rats was taken and HE staining was per⁃ formed to observe the pathological changes in the lung tissues under light microscope，and pathological score of lung injury was performed. The middle and superior lobes of right lung in the rats were homogenized in ice bath，and the supernatant was extracted by centrifugation. The content of TNF-α，IL-1β，intercellular adhesion molecule-1（ICAM-1），and vascular cell adhesion molecule-1（VCAM-1）in the lung tissues was determined by ELISA. The inferior lobe of right lung was tak⁃ en and fully lysed with RIPA lysate. Cytoplasmic protein and nuclear protein were extracted according to the instructions of cytoplasmic nucleoprotein extraction kit. The content of NF-κB in the cytoplasm and nucleus was determined by ELISA. Results Compared with the control group，PO2 of abdominal aorta and cytoplasmic NF-κB in the lung tissues significant⁃ ly decreased in the model group and celastrol group，while the W/D ，the content of TNF-α，IL-1β，ICAM-1，and VCAM-1 in the lung tissues and NF-κB in nucleus，and pathological score of lung injury significantly increased（all P<0. 05）. Com⁃ pared with the model group，PO2 of the abdominal aorta，NF-κB in cytoplasm of the lung tissues significantly increased in the celastrol group，while the W/D，the content of TNF-α，IL-1β，ICAM-1，and VCAM-1 in the lung tissues and NF-κB in nucleus，and pathological score of lung injury significantly decreased（all P<0. 05）. Compared with the control group， the alveolar hyperemia and bleeding were obvious in the model group，accompanied by a large number of inflammatory cell infiltration，and the alveolar structure collapsed and the contour was not clear. However，compared with the model group， the alveolar hyperemia and bleeding were significantly reduced in the celastrol group，and a small amount of inflammatory cell infiltration was observed in the alveolar，and the alveolar structure was clearly visible. Conclusion Celastrol can inhibit LPS-induced ALI in sepsis rats，and the mechanism may be related to the inhibition of nuclear translocation of NF-κB，thus inhibiting the content of inflammatory cytokines in rats. [ABSTRACT FROM AUTHOR]