Background: This study aimed to investigate the involvement of lncRNA CTBP1-AS2 in the progression of diabetic nephropathy (DN) by affecting high glucose (HG)-induced human glomerular mesangial cells (HGMCs). Methods: HGMCs were selected for the establishment of cell injury induced by HG. The expression of CTBP1-AS2, miR-155-5p and FOXO1 was detected by real-time PCR and western blotting. The target association between miR-155-5p and CTBP1-AS2 or FOXO1 was confirmed by dual-luciferase reporter assays. Cell proliferation and oxidative stress were revealed by CCK-8 colorimetry, and the measurement of reactive oxygen species (ROS) and the activities of antioxidant enzymes. Extracellular matrix (ECM) protein accumulation and the production of inflammatory cytokines were investigated by western blotting and ELISA. Results: The expression of CTBP1-AS2 was downregulated, and miR-155-5p was highly expressed in peripheral blood of DN patients and HG-treated HGMCs. Further investigation revealed that CTBP1-AS2 overexpression inhibited proliferation, oxidative stress, ECM accumulation and inflammatory response in HG-induced HGMCs. Mechanical analysis revealed that CTBP1-AS2 regulated FOXO1 expression via sponging miR-155-5p. Rescue experiments demonstrated that miR-155-5p overexpression or FOXO1 inhibition reversed the effects of CTBP1-AS2 in HG-stimulated HGMCs. Conclusion: Taken together, this study revealed CTBP1-AS2 attenuated HG-induced HGMC proliferation, oxidative stress, ECM accumulation, and inflammation through miR-155-5p/FOXO1 signaling. (C) 2020 Elsevier Inc. All rights reserved.