Objective To investigate whether the vascular endothelial growth factor-A (VEGF-A) inhibitor sFLT- 1(soluble fms-like tyrosin kinase-1)can reverse renal dysfunction in type 1 diabetic mice by inhibiting vascular endothelial cell activation and inflammation. Methods Twenty-five eight-week-old C57BL/ 6 female mice were divided into two groups:two groups treated for 5 weeks: healthy control group (n= 5) and diabetic group (n= 5), and three groups for 15 weeks: healthy control group (n= 5), diabetic group (n= 5), control+sFLT-1 treatment group (n= 5), diabetic+ sFLT-1 treatment group (n= 5). The model of type 1 diabetes was established by intraperitoneal streptozotocin (75 mg / kg) injection. The treated mice received sFLT-1 at the sixth week after the establishment of the model. Renal pathological damage, macrophage infiltration, glomerular endothelial cell activation and inflammation were observed before and after sFLT-1 treatment. Results Compared with the model group, sFLT-1 transfection significantly reduced the content of the glomerular mesangial matrix (glomerular type IV collagen) (P< 0.001), glomerular macrophage infiltration (P< 0.001), glomerular endothelial cell activation (P< 0.001) and the glomerular tumor necrosis factor-α level (P< 0. 001), and thus significantly inhibited diabetic renal injury. Additionally, sFLT-1 reduced the activation of endothelial cells induced by VEGF-A in vitro (P< 0.001). Conclusions sFLT-1 may reduce endothelial activation and glomerular inflammation by inhibiting VEGF-A, and finally reverse diabetes-related renal damage, which is a new direction of treatment for diabetic nephropathy.