〔Abstract〕 Objective To investigate whether Andrographolide(AG) can alleviate intestinal injury in sepsis by activating the SLC7A11/GPX4 axis in ferroptosis. Methods Forty rats were randomly divided into sham group(sham group), sepsis group(CLP group), AG low, medium and high dose groups(5, 10 and 20 mg/kg). HE staining was used to observe the pathological changes of Intestinal tract. ELISA method was used to determine Interleukin 6(IL-6), tumour necrosis factor α(TNF-α), intestinal fatty acid binding protein(I-FABP), D-lactate content. The mechanism of ferroptosis was explored with AG high dose group(AG20 group), forty rats were randomly divided into sham group, CLP group, ferroptosis inhibitor(Fer-1) group, AG20+Fer-1 group. HE staining and transmission electron microscopy were used to observe the pathological changes of Intestinal tract. The kits were used to determine oxidative stress MDA, GSH levels and Fe3+content. Western blot was used to detect the protein levels of solute carrier family 7 member 11(SLC7A11),glutathione peroxidase 4(GPX4), and ferritin heavy polypeptide 1(FTH-1). Results Compared with the sham group, the CLP group showed severe morphological damage to the small intestine, with significantly higher levels of inflammation, I-FABP and D-lactate(allP<0.05), the AG group reversed these changes in a concentration-dependent manner(allP<0.05). Compared with the CLP group, the AG20 and Fer-1 groups showed improved pathological damage to the small intestine, with lower levels of MDA and Fe3+and higher levels of GSH, SLC7A11, GPX4 and FTH-1 protein expression increased(allP<0.05), and pathological injury and oxidative stress were reduced in the AG20+Fer-1 group, and SLC7A11, GPX4 and FTH-1 protein expression increased more significantly(allP<0.05). Conclusion The mechanism by which AG attenuates intestinal injury in sepsis may be related to SLC7A11/GPX4 axis activation in ferroptosis.