Diabetic neuropathic pain is the most common symptom of diabetic neuropathy. The pathogenesis of diabetic neuropathic pain is quite complex, and existing drugs for the treatment of this complication are known to have limited efficacy. Therefore, it is desirable to identify novel therapeutic targets involved in the development and maintenance of diabetic neuropathic pain. Against this background, we found that the expression of a disintegrin and metalloproteinase 17 (ADAM17), a membrane-bound enzyme that cleaves extracellular portions of transmembrane proteins, was markedly increased in the spinal cord of leptin receptor-deficient db/db mice, a model of type 2 diabetes. Thus, we investigated the role of this molecule in diabetic neuropathic pain. In this study, the von Frey filament test and Hargreaves test were used to assess tactile and thermal hyperalgesia, respectively. The db/db mice showed marked tactile and thermal hyperalgesia at 9 weeks of age. In addition, the expression of pro- and mature-ADAM17 in the spinal cord of db/db mice were significantly increased at 9 weeks of age. Intrathecal injection of the ADAM17 inhibitor TAPI-1 and DNA-modified siRNA against ADAM17 (dsRDC) both significantly suppressed tactile and thermal hyperalgesia observed in db/db mice. Since ADAM17 was expressed on neurons and microglia in the dorsal horn of the spinal cord, upregulation of ADAM17 on these cells is suggested to be involved in the development of painful diabetic neuropathy.