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Background: Diabetic neuropathy (DN) is a prevalent complication of diabetes mellitus characterized by pain and inflammation. Long non-coding RNAs (lncRNAs) have been associated with DN. This study aimed to investigate transcript levels of Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), microRNA (miR)-1-3p, and C-X-C motif chemokine receptor 4 (CXCR4) in the DN patients and type 2 diabetes mellitus (T2DM) cases without neuropathy. Methods: Here, 20 cases with DN and 20 T2DM subjects without neuropathy (as the control group) were included. Total RNA was extracted from peripheral blood mononuclear cells (PBMCs) of all participants. The expression levels of targets were evaluated by Real-time-PCR. Results: Results showed that MALAT1 (Fold change = 2.47, P = 0.03) and CXCR4 (Fold change = 1.65, P = 0.023) were significantly upregulated, while miR-1-3p was downregulated (Fold change = 0.9, P = 0.028) in whole blood samples from DN patients compared to the control group. A significant correlation was found between transcript levels of MALAT1 and CXCR4 (rho = 0.84; P < 0.0001). Conclusions: This study suggests a possible involvement of the MALAT1/miR-1-3p/CXCR4 axis in the pathogenesis of DN.