Abstract: To observe the efficacy of different dose of mecobalamintherapy combined with lipo-prostaglandin E1 (Lipo PGE1) on diabetic peripheral neuropathy (DPN). Methods: Ninety-two patients with DPN were randomly assigned into high-dose of mecobalamin group (A group, n=31), regular-dose of mecobalamin group (B group, n=31) and control group (C group, n=30). All patients were treated with alimentary control, oral blood glucose lowering drugs or insulin injection treatment, and intravenous injection of Lipo PGE1. In addition, mecobalamin 1 000 靏 intramuscular injection once a day, mecobalamin 500 靏 intramuscular injection q.o.d, and vitamin B12 0.5 mg intramuscular injection once a day were given to group A, B and C, respectively. The duration of treatment were 4 weeks for all groups. Efficacy and nerve conductive velocity were assessed for comparison. Results：The mecobalamin significantly increased the excellence rate and total effective rate in a dose-dependent manner treating DPN, with 65% and 97% in Group A, 39% and 84% in Group B, 17% and 57% in Group C. Furthermore, mecobalamin therapy groups showed significantly greater improvement in conduction velocities of motor and sensory nerves than the control group (P<0.01). One case of mild gastrointestinal symptom in Group A, one case of dizziness and one case of transient phlebitis in Group B were reported during the treatment, and all were resolved after withdrawal. Conclusion：Combination of mecobalamin and Lipo PGE1 has a curative effect for DPN. Furthermore, high dose mecobalamin is better than regular dose.