Abstract：Objective：To observe the clinical effect of hot compressing at Zusanli (ST36) with Chinese medicine hot packages combined with Mecobalamine on senile diabetic perineuropathy (DPN) with qi deficiency and blood stasis syndrome. Methods： A total of 72 cases of senile DPN patients with qi deficiency and blood stasis syndrome were selected and divided into Group A， Group B， and Group C according to the random number table method，with 24 cases in each group. Group A was treated with hot compressing at Zusanli with Chinese medicine hot packages combined with Mecobalamine，Group B was treated with Mecobalamin alone， and Group C was treated with hot compressing at Zusanli with Chinese medicine hot packages alone. All the three groups were treated for 14 days continuously. Compared the clinical efficacy，Ankle Brachial Index (ABI) values，Numerical Rating Scale (NRS) scores，Toronto Clinical Scoring System (TCSS) scores， 36-item Short-Form healthy survey (SF-36) scores， traditional Chinese medicine (TCM) syndrome scores， motor nerve conduction velocity (MCV)， sensory nerve conduction velocity (SCV)，oxidative stress indexes，and hemorheological indexes in the three groups. Results：At 14 days of treatment (T3)， the total effective rate was 91.67% in Group A， higher than that of 66.67% in Group B and 62.50% in Group C (P＜0.05). At three days of treatment (T1)，the ABI values and SF-36 score in Group A were increased when compared with those before treatment (T0) (P＜0.05)，and the NRS and TCSS scores were decreased when compared with those at T0 (P＜0.05)； there was no significant difference in ABI values and scores of NRS， TCSS and SF-36 between Group B and Group C when compared with those in the same group at T0 (P＞0.05). At seven days of treatment (T2)， all the three groups showed an increase in ABI values and SF-36 scores when compared with those at T1 (P＜0.05)，a decrease in NRS and TCSS scores when compared with those at T1 (P＜0.05). At T3，all the three groups showed an increase in ABI values and SF-36 scores when compared with those at T2 (P＜0.05)， a decrease in NRS and TCSS scores when compared with those at T2 (P＜0.05). After treatment， the ABI values， and SF-36 scores in Group A were higher than those in Group B and Group C at each time point (P＜0.05)， and NRS and TCSS scores in Group A were lower than those in Group B and Group C at each time point (P＜0.05). At T3，the TCM syndrome scores，serum plasminogen activator inhibitor-1 (PAI-1) levels， hematocrit， plasma viscosity， whole blood low shear viscosity， and whole blood high shear viscosity levels in all the three groups were decreased when compared with those at T0 (P＜0.05)， and MCV，SCV，serum superoxide dismutase (SOD) and brain-derived neurotrophic factor (BDNF) levels were increased when compared with those at T0 (P＜0.05)；the TCM syndrome score，serum PAI-1 level，and the above four hemorheological indicators in Group A were all lower than those in Group B and Group C (P＜ 0.05)， and the serum SOD and BDNF levels were higher than those in Group B and Group C (P＜0.05). Conclusion： The hot compressing at Zusanli with Chinese medicine hot packages combined with Mecobalamine has a good therapeutic effect on senile DPN with qi deficiency and blood stasis syndrome， which can improve oxidative stress and hemorheological indicators，effectively alleviate patients' pain and neuropathy，and improve their quality of life.