Objective This study aims to monitor the mRNA ratio of podocin to nephrin (PNR) in glomerular podocytes of early diabetic kidney disease (DKD) rat models. The feasibility of using PNR as an early diagnostic indicator for DKD was evaluated by comparing it with the urinary albumin-to-creatinine ratio (U-ACR). Additionally, the early intervention effects of valsartan and fosinopril sodium on DKD were compared. Methods The DKD rat model was established by caudal intravenous injection of streptozotocin (STZ) at a dosage of 60 mg/kg. The early changes in PNR and U-ACR were monitored and compared, followed by timely intervention with valsartan and fosinopril sodium. Hematoxylin and eosin staining (HE) was used to observe glomerular structure, while transmission electron microscopy examined the ultrastructure of glomerular podocytes. ResultsPNR reached the critical value(≥1) on day 9 after modeling, earlier than U-ACR, which reached the critical value(≥30 mg/g) on day 15. Intervention with valsartan and fosinopril sodium on day 9 after modeling significantly reduced U-ACR (P < 0.05), with low-dose valsartan showing better results than high-dose (P>0.05), while high-dose fosinopril sodium outperformed low-dose (P>0.05). Both low doses of valsartan and fosinopril sodium significantly reduced PNR (P<0.05), with no significant effect observed for high doses. The interventions with valsartan and fosinopril sodium improved and maintained glomerular structure and podocyte arrangement. ConclusionPNR changes earlier than U-ACR, indicating its potential as an early diagnostic marker for DKD in rats. Early intervention with valsartan and fosinopril sodium demonstrates a therapeutic effect on DKD in rats.