Objective:To investigate the protective effects of Elabela(ELA) on the renal injury of db/db mice and its possible mechanism.Methods:Sixteen eight-week-old male db/db mice were intraperitoneally injected with ELA(5 mg·kg -1·day -1) or equivalent normal saline( n=8) for 8 weeks. Eight age-matched male db/m mice received equivalent normal saline injection as normal control. At the end of the experiment, blood and urine samples were obtained for HbA 1C and urinary albumin/creatinine(ACR) measurements. Immunohistochemistry was used to observe the expression of ELA. Histopathological changes in kidney tissue were observed by HE staining and Masson staining. The levels of collagen type Ⅳ(Col-Ⅳ) and transforming growth factor-β1(TGF-β1) as well as Yes-associated protein(YAP) phosphorylation in kidney tissue were examined by western blot. Results:Immunohistochemistry results showed that ELA expression was decreased in the renal tissue of db/db mice as compared with that of db/m mice( P<0.05). After ELA treatment, ACR and blood pressure were markedly decreased in db/db mice( P<0.05), but without significant changes in the body weight and HbA 1C. Renal tubular epithelial cells edema, basement membrane thickening, and increased collagen fiber in db/db were improved by ELA administration. Compared with db/m mice, the levels of TGF-β1 and Col-Ⅳ expression, as well as YAP phosphorylation were significantly increased in renal tissue of db/db mice(0.98±0.08 vs 0.68±0.10, 1.10±0.14 vs 0.51±0.08, 3.38±0.72 vs 0.81±0.13, all P<0.05), which were down-regulated after ELA administration(0.80±0.06, 0.51±0.05, 2.21±0.22, all P<0.05). Conclusion:ELA may improve the renal injury of db/db mice by regulating the signaling pathway of YAP, thereby delaying the development of diabetic nephropathy.