The major findings of our study are that (1) RANKL and RANK are overexpressed in kidneys of mice with type 2 DN; (2) the NF-κB pathway is activated in DN; (3) Irb treatment alleviates diabetes-induced renal dysfunction, podocyte injury, and MCP-1 expression; and (4) the beneficial effects of Irb in DN are associated with its ability to suppress RANKL/RANK and the downstream NF-κB pathway. The gene discussed is TNFRSF11A; the disease is diabetes mellitus.