Abstract： Objective:To observe the mechanism of hyperbaric oxygen combined with lipoic acid in treating diabetic foot patients, and analyze its preventive effect on amputation as the adverse outcome.Methods:A total of 84 patients with diabetic foot admitted to the Department of Endocrinology of Linyi Central Hospital from June 2016 to June 2019 were selected as research objects and randomly divided into control group ( n=42) and observation group ( n=42). The patients in the control group received intravenous infusion of lipoic acid (0.6 g/250 ml, 1 time/d) on the basis of conventional treatment, while the patients in the observation group received hyperbaric oxygen therapy on the basis of the treatment in the control group. The levels of hypoxia inducible factor-1 (HIF-1α), endothelin-1 (ET-1), nitric oxide (NO) and vascular endothelial growth factor (VEGF) in serum before and after treatment were compared between the two groups. The occurrence of amputation as the adverse outcome was also recorded. Results:After treatment, the levels of HIF-1α, ET-1, NO, and VEGF in both groups decreased, and the levels of HIF-1α, ET-1, and VEGF in the observation group were significantly lower than those of the control group ( P<0.05). The incidence of amputation as the adverse outcome in the observation group (9.52%) was lower than that of the control group (21.43%). Analysis of the receiver operating characteristic (ROC) curve showed that the threshold value of HIF-1α, ET-1/NO ratio, and VEGF for predicting amputation as the adverse outcome were 317.5 pg/ml, 1.977, and 29.0125 pg/ml, respectively. The specificity of HIF-1α for predicting amputation occurrence was 85.9%, which was better than those of ET-1/NO ratio (80.3%) and VEGF (76.4%). Conclusion:Hyperbaric oxygen combined with lipoic acid can significantly reduce the levels of HIF-1α, ET-1, NO, and VEGF in patients with diabetic foot. HIF-1α has a relatively high accuracy in predicting the occurrence of amputation, which can help to reduce or prevent the occurrence of amputation as the adverse outcome.