Stromal cell derived factor (SDF)-1 is a unique pleiotropic chemokine that mediates several biological and pathological functions through binding with its cognate receptor CXCR4. The SDF-1/CXCR4 axis typically exhibits a nephroprotective role, where it largely contributes to renal development and homeostasis. However, it was also reported to play an essential regulatory role in the initiation and development of diabetic kidney disease (DKD); yet, whether it is renoprotective or detrimental remains unclear. This study aimed to assess the prognostic capacity of circulating stromal cell-derived factor (SDF)-1 for diabetes-induced tubular atrophy. Thirty male Sprague Dawley rats (200-250gm) were allocated into diabetic (n=20) and sham (n=10) groups. Diabetes was induced by a single dose of 65 mg/kg STZ, then diabetic animals were categorized into treated group receiving 2-8U Mixtard®30 daily, and untreated group (n=10/each). Blood glucose, renal functions, circulating SDF-1, and inflammatory markers were weekly assessed, and renal expression of SDF-1/CXCR4 was profiled by real-time PCR. Insulin treatment ameliorated hyperglycemia and normalized renal functions and inflammation, while the untreated animals exhibited the typical course of hyperglycemia-associated nephropathy. Circulating SDF-1 levels were significantly lower in both diabetic groups than in sham (P<0.05), but persistently higher in the untreated animals (P<0.0001). Renal SDF-1/CXCR4 expression was 1.51, 2.11, and 2.76, 1.45 fold higher in untreated animals relative to non-diabetic and treated animals; respectively. ROC curve analyses of plasma/urinary SDF-1 in diabetic groups showed AUC of 0.9568 and 0.9793; respectively with cut-off values 72.78 pg/mL and 0.7182 pg/mg Cr; respectively. Both thresholds showed predictive potentials with 81.82-83.33% sensitivity and 100% specificity. In conclusion, plasma/urinary SDF-1 levels showed considerable prognostic potential for early tubular atrophy during DKD.