Background and Aims Stent implantation is one of the main treatments for lower extremity arteriosclerosis obliterans (ASO). It effectively restores vascular patency and improves clinical symptoms, but some patients experience in-stent restenosis within one year after surgery. In-stent restenosis can lead to poor prognosis for patients, making it crucial to understand the pathological mechanisms influencing restenosis after surgery for ASO. Serum interleukin 8 (IL-8) and vascular endothelial growth factor (VEGF) are indicators of inflammation and endothelial function, respectively, and are closely related to the occurrence of ASO. However, it is unclear whether they are associated with in-stent restenosis after stent implantation for ASO. Therefore, this study was conducted to investigate the association of IL-8 and VEGF levels with in-stent restenosis in ASO patients within one year after stent implantation, and establish a nomogram model to predict in-stent restenosis within after stent implantation.Methods A total of 100 ASO patients who received stent implantation at Department of Vascular Surgery, Nanyang First People's Hospital between January 2020 and October 2022 were selected for the study. Patients were followed up for one year after-surgery and divided into restenosis and non-restenosis groups based on follow-up results. Demographic characteristics, postoperative serum IL-8 and VEGF levels, and other relevant variables were collected. Univariate and Logistic regression analyses were used to identify risk factors for in-stent restenosis within one year after stent implantation. A nomogram model was constructed based on these risk factors to predict the risk of in-stent restenosis within one year after stent implantation, and the predictive model was validated.Results Four patients were lost to follow-up, resulting in a loss rate of 4.00% (4/100). Among the 96 patients, 29 experienced in-stent restenosis, with an in-stent restenosis rate of 30.21% (29/96). Logistic regression analysis revealed that age ≥60 years (OR=4.191), Fontaine stage Ⅳ (OR=2.863), complete occlusion (OR=2.445), lower extremity vascular lesion length ≥7.15 cm (OR=3.343), postoperative IL-8 ≥1.02 ng/mL (OR=6.482), and postoperative VEGF ≥158.37 pg/mL (OR=10.402) were independent risk factors for in-stent restenosis within one year after stent implantation (all P<0.05). Validation of the nomogram prediction model constructed based on these factors showed that the calibration curve was close to the ideal curve; the C-index was 0.857 (95% CI=0.785-0.952). The ROC curve results showed that the area under the ROC curve for predicting in-stent restenosis within one year after stent implantation was 0.852 (95% CI=0.631-0.979), with sensitivity and specificity of 92.50% and 78.40%, respectively.Conclusion Postoperative serum IL-8 and VEGF levels are closely related to the incidence of in-stent restenosis in ASO patients. Higher postoperative serum IL-8 and VEGF levels indicate a higher risk of in-stent restenosis. The nomogram model based on these findings can assist clinicians in providing better treatment and follow-up plans for ASO patients.