Aim To detect the levels of serum soluble cluster differentiation 163 (sCD163) and heme oxygenase-1 (HO-1) in patients with lower extremity atherosclerotic occlusive disease (LEAOD), and to explore the correlation between the levels of sCD163, HO-1 and restenosis after intervention. Methods From May 2016 to February 8,5 patients with LEAOD who were given interventional therapy in the Vascular Surgery Department of Nanyang Central Hospital were selected as the study object. According to the reexamination results, they were divided into two groups:restenosis group (n=47) and non restenosis group (n=68). Enzyme linked immunosorbent assay (ELISA) was used to detect the levels of serum sCD163 and HO-1 in each group. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of serum sCD163 and HO-1 levels for restenosis in patients with LEAOD, and Logistic regression was used to analyze the influencing factors of restenosis in patients with LEAOD. Results The levels of serum sCD163 and HO-1 in restenosis group were significantly higher than those in non restenosis group (P＜0.05). The results of ROC showed that the AUC of serum sCD163 and HO-1 in the diagnosis of restenosis after LEAOD was 0.863 and 0.736 respectively, and the cut off value was 660.792 μg/L and 15.067 μg/L respectively, at this time, the corresponding sensitivity was 80.9% and 57.4% respectively, and the specificity was 77.9% and 92.6% respectively. The AUC of serum sCD163 combined with HO-1 in the diagnosis of restenosis after LEAOD was 0.896, and the corresponding sensitivity and specificity were 87.2% and 79.4%, respectively. Logistic analysis showed that the high levels of serum sCD163 and HO-1 were independent risk factors for restenosis after LEAOD intervention. Conclusion The levels of sCD163 and HO-1 in serum of patients with restenosis after LEAOD intervention are significantly increased, and both of them participate in the occurrence and development of restenosis after LEAOD intervention, suggesting that sCD163 and HO-1 may be potential biological indicators for early diagnosis and disease assessment of patients with restenosis after LEAOD intervention.