AIM: Peripheral neuropathy is one of the most common diabetic complications in a chronic process in the absence of glycemic control, and the pathogenesis of diabetic peripheral neuropathy (DPN) is not fully understood yet. Clinical experiments are on-going and also recent evidences indicates hope from in silico analysis. The aim of this study was to examine possible involvement of neuropeptides in DPN by using bioinformatics tools, by examining the expression levels of genes, known to have neuroendocrine functions through genome analyzes performed in sciatic nerve tissues obtained from diabetic rats. METHODS: GSE1477321 dataset obtained from GEO (Gene Expression Omnibus) database was re-examined for this research. In the dataset, sciatic nerve tissue samples (n=6) derived from normal and streptozotocin-induced diabetic Sprague-Dawley rats are recruited. After the gene expression levels in the dataset were re-analysed in the R program, gene set enrichment analyses were performed in Gene Ontology (GO) and ENRICHR tools. APPROACH FOR STATISTICAL ANALYSIS: Expression levels of genes, commonly implicated to play a role in neuroendocrine modulations, in GSE147732 dataset are re-analysed in R program. Based on Benjamini-Hochberg correction, adjusted p-values <0.05 were accepted as significant. RESULTS: Gene expression levels on the dataset indicated that neuropeptide Y (NPY), neuropeptide receptor 1Y and 2Y (NPY1R, NPY2R), proopiomelanocortin (POMC), pancreatic polypeptide receptor 1 (PPYR1), calcitonin receptor-like peptide (CALCRL), endothelin 1 (EDN1), vasoactive intestinal peptide (VIP), angiotensinogen (AGT), neurotensin receptor 1(NTSR1), parathyroid hormone 1 receptor (PTH1R), neuropeptide W (NPW), thyrotropin releasing hormone receptor (TRHR), chromogranin A (CHGA), adiponectin (ADIPOQ), resistin (RETN), neuromedin B (NMB), cerebellin 2 procursor (CBLN2), period homolog 1 and 2 (PER1 and PER2), clock homolog gene (CLOCK), chemokine (C-C motif) ligand 21, (C-X-C motif) ligand 12 and (C-X3-C motif) ligand 1 (CCL21, CXCL12, CX3CL1), galectin 1,5,8,9 (LGALS1, LGALS5, LGALS8, LGALS9) genes were down-regulated (p<0.05); and galanin (GAL), somatostatin receptor 3 (SSTR3), neuropeptide FF-amide peptide precursor (NPFF), adrenomedullin (ADM), endothelin 3 (EDN3), secretin (SCT), gastric inhibitory polypeptide (GIP), corticotropin releasing hormone receptor 2 (CRHR2), urocortin 2 (UCN2), tachykinin 1 (TAC1), neuromedin U (NMU), nerve growth factor receptor (NGFR) genes were up-regulated (p<0.05) in the diabetic group, compared with normal group. CONCLUSION: Results from this in silico analysis indicate imbalances in the expression levels (down- and up-regulation) of genes encoding neuropeptides known to be involved in many neuroendocrine process, implicating involvement of impaired neuroendocrine signalling in the pathogenesis of DPN. Keywords: Diabetic neuropathy, sciatic nerve, neuropeptides, gene expression, bioinformatics.