Objective To study the effect of quinocyclohexanone on diabetic nephropathy and the expression of angiotensin II (Ang II) and vascular endothelial growth factor (VEGF) in the kidneys of rats. Methods Forty 8-week-old healthy Sprague-Dawley rats were allocated to a control group ( n = 10) or used to establish model of diabetic nephropathy (DN) ( n =30). Having confirmed the presence of DN, n =10 rats with DN were randomly allocated to a model group and n =20 rats were administered quinocyclohexanone at 5 mg/ kg, 10 mg/ kg, 15 mg/ kg, or 30 mg/ kg,respectively. The control and the model groups were administered the same volume of saline. Urinary albumin excretion rate (UAER), glomerular filtration rate ( GFR), fasting blood glucose ( FBG), glycosylated hemoglobin ( HbA1c), insulin resistance index (HOMA-IR), 24-hour urinary microalbumin (24hU-mAlb), beta-2 microglobulin (beta-2-MG), blood urea nitrogen (BUN), renal mononuclear chemoattractant protein-1 (MCP-1) mRNA and agglutinin proteins, expression levels of oxidized low-density lipoprotein receptor (LOX-1) mRNA, Ang II and VEGF were compared among the groups. Results When the dose was 15 mg/ kg, the levels of Uaer and GFR in rats approached the normal levels of UAER and GFR. Therefore, it was considered that 15 mg/ kg was the appropriate dose. The following studies were conducted at the dose of 15 mg/ kg.. FBG, HbA1c, HOMA-IR, 24hU-mAlb, beta 2-MG, and BUN values in the model and quincyclohexanone groups were higher than those in the control group ( P < 0. 05). The renal expressions of MCP-1, LOX-1, Ang II, and VEGF in the model and quincyclohexanone groups was also higher than in the control group ( P < 0. 05). However, FBG, HbA1c, HOMA-IR, 24hU-mAlb, beta 2-MG, and BUN in the quincyclohexanone group were lower than in the model group ( P < 0. 05), as well the renal expression levels of MCP-1, LOX-1, Ang II, and VEGF ( P < 0. 05). Conclusions Quinocyclohexanone may ameliorate pathologic changes and defects in renal function in rats with dibetic nephropathy by inhibiting the expression of Ang II and VEGF. It appears to be renoprotective.