Objective To observe the effect of aralia saponins on the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) in the kidney of diabetic nephropathy mice. Methods After 10 days of adaptive feeding, 90 clean Kunming mice were randomly divided into the normal group (n=10) and 5 model groups (model group, positive drug benazepril intervention group, aralia saponins low, middle and high doses treatment groups). Excepted the normal group, the kidney damage model of type 2 diabetes mellitus in mice was induced by high-fat and high-sugar diet for one month plus disposable streptozotocin (STZ). The model was successfully constructed and killed after 6 weeks of treatment. A total of 25 mice failed to establish the model. And totally 55 mice were randomly divided into 5 groups with 11 mice in each group. The serum changes of blood urea nitrogen (BUN), serum creatinine (SCr), insulin, inflammatory factors interleukin-1α (IL-1α), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in each group were detected. The expression of vascular endothelial growth factor and MMP-9 protein in renal tissue were detected by immunohistochemistry and Western blot. Results Compared with the normal group, the levels of blood glucose, insulin, BUN, SCr, IL-1α, IL-6 and TNF-α in the model group were significantly increased (P<0.05). The above indexes were decreased in positive drug group and aralia saponins treatment groups. The contents of insulin, BUN and SCr in the high dose of aralia saponins group were significantly lower than those parameters in benazepril group (P<0.05). In addition, the contents of blood glucose, IL-1α, IL-6 and TNF-α in the three dose aralia saponins groups were significantly lower than those parameters in the benazepril group (P<0.05). Compared with the normal group, the expression level of VEGF protein in the model group was significantly higher (P<0.05), and the expression level of MMP-9 protein was significantly lower (P<0.05). Compared with the model group, both benazepril and aralia saponins can reduce VEGF (P<0.05), increase MMP-9 (P<0.05). In addition for VEGF and MMP-9, the high dose of aralia saponins group and benazepril group was basically same. Conclusions Aralia saponins can significantly reduce blood glucose, insulin and serum inflammatory factors, while downregulate VEGF and increase MMP-9 protein levels, thereby protecting the kidneys of diabetic nephropathy mice. Key words: ARALOSIDE; Diabetic nephropathies; Vascular endothelial growth factors; Matrix metalloproteinase 9; Mice