Abstract：Objective：To investigate the intervention effect of Ramipril combined with resveratrol on early glomerulosclerosis in diabetic kidney disease (DKD) rats. Methods：Sprague-Dawley (SD) rats were selected for the experiment， with 8 in the control group and 32 in the intraperitoneal injection of streptozotocin (STZ) to induce the construction of early DKD models. After successful modeling，rats in the control group were given 1 mL of phosphate buffer solution (PBS) by gavage every day. Rats with STZ- induced diabetes were divided into the following four groups：Group 1，1 mL PBS was given by gavage every day. Group 2，received 15 mg/kg of resveratrol daily. Group 3，given 10 mg/kg of Ramipril daily. Group 4 was treated with resveratrol (15 mg/kg) and Ramipril (10 mg/kg) daily for 10 consecutive days. All rats were anesthetized with 5% isoflurane for cardiac blood collection and euthanized，and tissue samples were collected for further analysis. Results：STZ-induced DKD rats (group 1) showed early symptoms of microalbuminuria and increased glomerulosclerosis/glomerular ratio (P＜0.05). The glomerulosclerosis/ glomerular ratio did not significantly decrease in the second group，while the glomerulosclerosis/glomerular ratio decreased in the third and fourth groups (P＜0.05). There was no difference in the expression of TGF-β signaling pathway related proteins with mediating tissue fibrosis in the kidneys between groups. However， in the STZ-induced DKD group，the levels of RhoA and ROCK2 proteins in the kidneys were increased. After treatment with Ramipril or the combination of Ramipril and resveratrol，the expression levels of RhoA and ROCK2 proteins were significantly decreased to levels close to the control group. Conclusion：Early glomerulosclerosis in rats with DKD is mainly mediated through the RhoA/ROCK2 signaling pathway. The use of Ramipril or the combination of Ramipril and resveratrol for treatment can effectively reduce the expression levels of RhoA and ROCK proteins，alleviate renal fibrosis，and reveal that glomerulosclerosis at this stage of the disease is reversible.