Reducing mortality from septic shock and damage to multiple organs from systemic inflammation and endotoxic hypoglycaemia is an unmet medical need. In the current investigation, we evaluated the effects of acupoint catgut-embedding therapy (ACET) on lipopolysaccharide (LPS)-induced septic shock in mice. Four groups of male C57J/B6 mice were examined: (1) sham without LPS, (2) ACET without LPS, (3) sham with LPS, and (4) ACET with LPS. ACET was performed once a week for 2 weeks at the following acupoints: Shui Fen (Ren-9), Qihai (Ren-6), and bilateral Siman (Ki-14). During week 3, mice received saline or LPS (15 mg/kg intraperitoneally). Biochemical parameters, protein and gene expression levels, and survival rates were analysed after saline or LPS administration. As a result, LPS-induced hypotension was unaffected, but the increases in lactic dehydrogenase, creatinine, and interleukin-17 levels were attenuated by ACET. Strikingly, ACET pretreatment completely prevented mortality in septic mice. At the molecular level, both LPS-induced IκB-αdegradation and inflammation were attenuated. Prevention of LPS-induced hypoglycaemia was associated with the regulation of hypothalamic 5' AMP-activated protein kinase and hepatic phosphoenolpyruvate carboxykinase. The synergistic actions of ACET prevented mortality in septic mice. In conclusion, the current investigation revealed the important medicinal value of ACET for the reduction of mortality during sepsis.