GLP-1-based treatment improves glycemia through stimulation of insulin secretion and inhibition of glucagon secretion. Recently, more and more findings showed that GLP-1 could also protect kidney from diabetic nephropathy. Most of these studies focused on glomeruli, but the effect of GLP-1 on tubulointerstitial and tubule is not clear yet. In this study, we examined the renoprotective effect of recombinant human GLP-1 (rhGLP-1), and investigated the influence of GLP-1 on inflammation and tubulointerstitial injury using diabetic nephropathy rats model of STZ-induced. The results showed that rhGLP-1 reduced urinary albumin without influencing the body weight and food intake. rhGLP-1 could increased the serum C-peptide slightly but not lower fasting blood glucose significantly. In diabetic nephropathy rats, beside glomerular sclerosis, tubulointerstitial fibrosis was very serious. These lesions could be alleviated by rhGLP-1. rhGLP-1 decreased the expression of profibrotic factors collagen I, alpha-SMA, fibronectin, and inflammation factors MCP-1 and TNF alpha in tubular tissue and human proximal tubular cells (HK-2 cells). Furthermore, rhGLP-1 significantly inhibited the phosphorylation of NF-kappa B, MAPK in both diabetic tubular tissue and HK-2 cells. The inhibition of the expression of TNF alpha, MCP-1, collagen I and alpha-SMA in HK-2 cells by GLP-1 could be mimicked by blocking NF-kappa B or MAPK. These results indicate that rhGLP-1 exhibit renoprotective effect by alleviation of tubulointerstitial injury via inhibiting phosphorylation of MAPK and NF-kappa B. Therefore, rhGLP-1 may be a potential drug for treatment of diabetic nephropathy. (C) 2017 Elsevier Inc. All rights reserved.