Objective: To explore the clinical efficacy and mechanism of Xuefu Zhuyu decoction in the treatment of arteriosclerosis obliterans of lower limbs. How: Forty patients with lower extremity arteriosclerosis obliterative disease treated in our department from January 2022 to January 2023 were selected. The control group received beprost sodium, and the treatment group received Xuefu Zyu decoction and beprost sodium. The changes of blood biochemistry, SOD, MDA, ox-LDL, NO levels, ABI and intermittent claudication distance before and after treatment were observed and compared between the two groups. Results: Both groups were successfully treated. There were no significant differences in age, gender, blood glucose level, blood lipid level and blood pressure between the two groups at baseline, and no significant differences in blood glucose level and blood lipid level between the two groups before and after treatment. However, although the diastolic blood pressure was not significantly different before and after treatment, the systolic blood pressure was significantly lower than that before treatment. SOD after treatment was higher than that before treatment (P<0.05). After treatment, SOD in treatment group was significantly higher than that in control group (P<0.05). MDA after treatment was significantly lower than that before treatment. After treatment, MDA in the treatment group was significantly lower than that in the control group (P<0.05). ox-LDL decreased after treatment, and the difference before and after treatment was statistically significant (P<0.01). The NO level in the treatment group was significantly increased before and after treatment (30.29±9.12 vs 53.79±11.15umol/L,P=0.000), while the NO level in the control group was also increased after treatment (30.08±9.06 vs 39.95±14.11umol/L,P=0.012). Further analysis showed that the serum NO level in the treatment group was significantly higher than that in the control group after treatment (P=0.026). The left ABI level was significantly improved in the treatment group before and after treatment, while the right ABI level was improved in both groups after treatment. For intermittent claudication distance, we found that the increase of intermittent claudication distance after treatment was significantly higher than that before treatment in both groups. Conclusion: We found that Xuefu Zhuyu decoction is effective and safe in the treatment of lower limb arteriosclerosis obliterans, explored the anti-oxidative stress pathway and its possible mechanism, and provided a new idea for the drug treatment of lower limb arteriosclerosis obliterans.