On the track of the crucial role for Notch1 and TLR4 signaling pathways in regulation of diabetic neuropathy, this study aims to investigate the involvement of specific interactions of Notch1 and TLR4 signaling pathways by using both streptozotocin (STZ)-induced diabetic rat model in vivo and cultured DRG neurons under high glucose challenge in vitro. This evidence concerns the gene NOTCH1 and diabetic neuropathy.