The current study has provided extensive evidence that endothelial cell-specific NOX5 expression further exacerbates renal injury in diabetes, as reflected by an increase in albuminuria, EMT-related factors, and renal fibrosis, as well as enhancing inflammation and activating ROS-sensitive pathways, even in the absence of NOX4 in the context of STZ-induced diabetes. Here, NOX5 is linked to diabetes mellitus.