Abstract: OBJECTIVE To systematically evaluate the efficacy and safety of high-dose mecobalamin in the treatment of diabetic peripheral neuropathy, and to provide a reference for the rational drug use and policy evaluation of off-label use.METHODS Retrieved from the Cochrane Library, PubMed, Embase, Wanfang, CNKI and Sinomed database from the inception to May 2018, randomized controlled trials(RCTs) about of high-dose mecobalamin(test group) compared with conventional-dose mecobalamin(control group) in the treatment of diabetic peripheral neuropathy was collected. After the data extraction and evaluation of methodological quality of RCTs, meta-analysis was conducted by using RevMan 5.3 software. RESULTS A total of 10 RCTs were included, involving 747 patients. The results of meta-analysis showed that motor nerve conduction velocity of sural nerveMD=1.61, 95%CI(0.26, 2.96), P=0.02, sensory nerve conduction velocity of sural nerveMD=2.73, 95%CI(2.07, 3.39), P<0.001, the total effective rate of treatmentRR=1.16, 95%CI(1.09, 1.23), P<0.001 of test group were significantly superior to those of control group, with statistical significance. The subgroup analysis showed that the total effective rate of high-dose mecobalamin administered by once a day or twice a day was significantly higher in the test group than in the control group, with a statistically significant difference(P<0.001). The incidence of adverse reactions in the test group was slightly higher than that in the control group, and the difference was not statistically significant. CONCLUSION High-dose mecobalamin has better clinical efficacy and similar safety compared with conventional-dose of mecobalamin in the treatment of diabetic peripheral neuropathy.