In order to elucidate the epigenetic mechanism and explore new biomarkers for diabetes and diabetic nephropathy, circulating lncRNA and mRNA expression profiles of normal control, diabetes mellitus, and diabetic nephropathy patients were analyzed. Serum samples from diabetic nephropathy patients (DN), diabetes mellitus patients without microalbuminuria (DM), and healthy controls (N) were collected. Arraystar Human LncRNA/mRNA V3. 0 expression spectrum biochips were used for serum lncRNA and mRNA expression profile analysis. The urinary microalbumin/creatinine ratio and serum creatinine level were higher in diabetic nephropathy patients, and the estimated glomerular filtration rate (eGFR) was significantly decreased compared to that in diabetic patients and healthy controls (p< 0.05). Compared with healthy controls, 245 upregulated and 680 downregulated lncRNAs were identified in the serum of diabetic patients, and 45 and 813 lncRNAs were up-and downregulated in the serum of diabetic nephropathy patients compared with diabetic patients. Levels of lncRNA-ARAP1-AS2 gradually increased during the progression of diabetes and diabetic nephropathy (2.82 times in DM/N and 2.47 times in DN/DM), whereas those of lncRNA-ARAP1-AS1 gradually decreased (2.24 times in DM/N, 4.79 times in DN/DM). Additionally, mRNA levels of their target gene ARAP1 (ArfGAP with RhoGAP domain, ankyrin repeat, and PH domain 1) gradually increased (2.25 times in DM/N and 2.45 times in DN/DM). lncRNA-ARAP1-AS1 and ARAP1-AS2 enhanced ARAP1 mRNA expression and may be involved in the pathogenesis of diabetes and DN. Circulating lncRNA-ARAP1-AS1, ARAP1-AS2, and ARAP1 may serve as new biomarkers for diabetes and diabetic nephropathy.