Objective To investigate the effect of combination therapy of Gabapentin and Cobamamide in treatment of painful diabetic neuropathy (PDN).Methods A total of 96 patients with type 2 diabetes (T2DM) and PDN were enrolled in this study and randomly divided into control group (Con,n=32),Cobamamide group,(n=32),and Gabapentin+Cobamamide group,(n=32).FPG and HbA1c were actively controlled in each group.Con group was treated with vitamin B1.Clinical and biochemical data of all the subjects were collected.The degree of pain was assessed by visual analogue scale (VAS).The changes of median nerve,peroneal nerve motor nerve conduction velocity (MNCV),and sensory nerve conduction velocity (SNCV) were evaluated by EMG assessment.The assessment of sleep quality was done by Pittsburgh sleep quality index scale (PSQI).Results There was no significant differences of baseline MNCV,SNCV and the degree of pain among the three groups (P>0.05).After treatment,all the above index were improved in both Cobamamide group and Gabapentin+Cobamamide group.MNCV and SNCV were higher in Gabapentin+Cobamamide group than in Cobamamide group (P<0.05).There were no significantly improvement of MNCV and SNCV in Con group (P>0.05).Conclusion The combination therapy of Gabapentin and adenosine cobalt amine could reduce pain,improve nerve conduction velocity,and improve the quality of sleep.