Objective: To compare the clinical efficacy between acupuncture and intravenous administration of lipoic acid and alprostadil for distal symmetric multiple peripheral neuropathy of diabetes mellitus., Methods: Sixty patients were randomly divided into an acupuncture group (31 cases) and a medication group (29 cases). Patients in the two groups received basic treatment to control blood sugar within a safe range. On this basis, patients in the acupuncture group were treated with acupuncture at Geshu (BL 17), Weiwanxiashu (EX-B 3), Ganshu (BL 18), Pishu (BL 20), Shenshu (BL 23), Zusanli (ST 36), Taixi (KI 3), ashi points, etc. Patients in the medication group were treated with intravenous administration of lipoic acid (0.6 g) and alprostadil (10 mg). The treatment was given once a day, 10 days for a course of treatment; there was an interval of 2 days between courses, and totally 3 courses were given. The score of peripheral neuropathy of diabetes mellitus, the change of nerve conduction: velocity and clinical efficacy before and after treatment in the two groups were observed., Results: After treatment, the score of peripheral neuropathy was significantly reduced in the two groups (both P < 0.05), which was more significant in the acupuncture group (P < 0.05). After treatment, the sensory nerve conduction velocity (SNCV) and motor nerve conduction velocity (MNCV) of median nerve and common peroneal nerve were significantly increased in the two groups (all P < 0.05). Compared between two groups, the SNCV and MNCV of common peroneal nerve in the acupuncture group were significantly superior to those in the medication group (both P < 0.05); the MNCV of median nerve in the acupuncture group was significantly superior to that in the medication group (P < 0.05); the SNCV of median nerve in the acupuncture group was not significantly different from that in the medication group (P > 0.05). The total effective rate was 83.9% (26/31) in the acupuncture group, which was significantly superior to 62.1% (18/29) in the medication group (P < 0.05)., Conclusion: Acupuncture and conventional medication both have satisfied effects for distal symmetric multiple peripheral neuropathy of diabetes mellitus, and acupuncture is superior to medication on improving clinical signs of sensory disorder, reflection disturbance and muscle weakness, nerve conduction and clinical curative effect.