To reveal the expression and possible role of tribbles homolog 3 (TRB3) in the incidence of type 2 diabetic nephropathy, we used immunohistochemistry, real-time quantitative PCR, western blot analysis, and enzyme-linked immunosorbent assay (ELISA) to study the expression of TRB3, extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase (ERK1/2 MAPK), transforming growth factor β1 (TGF-β1), and collagen type IV in kidneys of db/db diabetic mice and in murine renal mesangial cells stimulated with high glucose. This evidence concerns the gene TRIB3 and type 2 diabetes nephropathy.