Diabetes mellitus (DM) is the third chronic disease that poses a serious threat to human health due to the impaired glycemic control, high medical cost and the prevalence of this disease is rising and reach 783 million by 2045 worldwide. Long non-coding RNA (LncRNA) has important role in regulating beta-cell function, glucose metabolism, insulin secretion, insulin resistance, additionally can regulate this function throughout their interactions with biomolecules like DNA, RNA and protein. LncRNA are transcripts longer than 200 nucleotides, transcribed by RNA polymerase II and they also 5′-capped, polyadenylated and spliced. they were initially considered as “junk-products” or noise of transcription without biological function as it of no significant protein-coding potential. LncRNAs can regulate gene expression at the epigenetic level, transcription and post transcriptional processing. the role of MALAT1 (metastasis-associated lung adenocarcinoma transcript 1, often referred to as NEAT2), XIST (X-inactive specific transcript) and NEAT1 (nuclear paraspeckle assembly transcript 1) and their underlying mechanisms regarding the progression of diabetes and its microvascular complication will be illustrated in this review.