Objectives: NADPH oxidase (NOX) is a major source of reactive oxygen species (ROS) that accelerates the development of diabetic kidney disease and chronic kidney disease. Among them, the most recently revealed role of NOX5 is receiving great attention in the kidneys. However, the role of NOX5 in chronic kidney disease is not well known yet. Therefore, this study tried to investigate the relationship between NOX5 and chronic kidney disease and the possibility of NOX5 as a treatment target for chronic kidney disease. Methods: We used podocyte-specific NOX5 tg (NOX5 tg) mouse to induce chronic kidney disease with 0.2% adenine diet for 2 weeks. Kidney function and structure were examined by urine albumin/creatinine ratio (ACR), blood urea nitrogen, periodic acid-Schiff, Masson's trichrome, and immunohistochemical stainings. Andin vitrostudies were conducted after generating podocytes genetically overexpressing NOX5.Cytoskeletone of podocytes was investigated by phalloidin staining. The influence of ROS to podocytes was also analyzed using 2’,7’dichlorofluorescin diacetate (DCF-DA). Results: NOX5 expression was markedly increased in renal glomerular podocytes in NOX5 tg mouse induced with CKD. Also, the expression of urinary NOX5 was even moreupsurged when NOX5 tg mouse was fed with adenine diet. And we confirmed an increase of ACR in adenine-induced NOX5 tg mouse, compared with adenine-induced WT mouse. In addition, podocyte cytoskeletal rearrangement was induced by ROS in podocytes by NOX5 overexpression in vitro. Conclusions: NOX5 can accelerate adenine-induced kidney injury, such as podocyte damage, and ROS production by NOX5-induced podocyte cytoskeleton rearrangement.Based on evidence that NOX5 can accelerate adenine-induced kidney injury, this study showed the possibility of NOX5 as a treatment target for chronic kidney disease.