Significant different levels of AQP1, AQP2 and CCL21 mRNA were found in DN patients compared to HCs (p < 0.05).Significant correlations were discovered between CCL21 mRNA and 24h proteinuria and eGFR (r = 0.8009, p < 0.0001; r = −0.5186, p = 0.0160, respectively).ROC-AUC analysis revealed an excellent diagnostic accuracy of CCL21 mRNA in distinction of both DN from DM patients and incipient DN patients from overt DN patients (AUC = 0.888, 95% CI 0.752–1; AUC: 1.0, 95% CI 1.0–1.0, both p < 0.0001). This evidence concerns the gene CCL21 and diabetes mellitus.