Objective To detect the expression change of ETFβ in diabetic nephropathy rats and study the role of ETFβ in fatty acid-induced apoptosis in renal tubules. Methods Diabetic nephropathy model was established by intraperitoneal injection of streptozotocin and unilateral nephrectomy. In vivo ETFβ expression was detected in renal cortex, as well as tubular injury evaluated. In vitro fatty acid-induced apoptosis in renal tubular cells NRK 52E model was established and ETFβ recombinant plasmid was constructed to be transfected into NRK 52E cells and furtherly to observe the effect of ETFβ over-expression on the fatty acid-induced apoptosis. Results In the rats model of diabetic nephropathy induced by streptozotocin injection and unilateral nephrectomy, ETFβ mRNA and protein expression were decreased as obvious tubular damage occurred. Fatty acids could induce apoptosis in NRK 52E, and ETFβ over-expression reduced the apoptosis. Conclusion The expression of ETFβ is decreased in diabetic nephropathy model, and ETFβ over-expression can reduce apoptosis induced by fatty acid in renal tubular cells.