Objective: To explore the feasibility of improving lower extremity arterial blood flow by pancreatic kininogenase combined with alprostadil in patients with diabetic foot (DF). Methods: Sixty-one patients with DF admitted to the hospital from May 2024 to May 2025 were selected and divided into observation group (n=31) and control group (n=30) by EXCEL to generate random numbers. The control group received alprostadil, while the observation group was combined with pancreatic kininogenase on the basis of the control group. The differences in clinical efficacy and lower extremity arterial hemodynamic indexes [ankle brachial index (ABI), superficial femoral artery resistance index (RI), superficial femoral artery peak blood flow velocity, superficial femoral artery blood flow] were compared between the two groups. The adverse reactions during treatment were recorded and compared. Results: Compared with control group, the clinical total effective rate was higher in observation group after 4 weeks of treatment (P<0.05). Both groups showed significantly increased ABI, superficial femoral artery peak blood flow velocity and superficial femoral artery blood flow volume compared to before treatment, with observation group demonstrating significantly higher values than control group (P<0.05). The superficial femoral artery RI was decreased significantly in both groups compared to before treatment, with observation group showing a significantly lower value than control group (P<0.05). During treatment, there was no significant difference in the occurrence of adverse reactions between the two groups (P>0.05). Conclusion: Pancreatic kininogenase combined with alprostadil in the treatment of DF can enhance the clinical efficacy, and significantly improve the lower extremity artery hemodynamic status, with good safety.