Abstract: Objective To explore the relationship between serum osteopontin(OPN) concentration and the progression of diabetic nephropathy(DN) and renal function. Methods From March 2019 to March 2021, 124 patients with type 2 diabetes mellitus(T2DM) were recruited and assigned into normal group(<30 mg/g, n=20), microgroup(30~300 mg/g, n=41), large group>300 mg/g and estimated glomerular filtration rateeGFR ≥ 90 mL· min^-1·(1.73m²) ^-1, n=30and renal function impairment groupeGFR <90 mL· min^-1·(1.73m²) ^-1, n=33according to urinary albumin/creatinine ratio(UACR). Another 40 healthy persons without T2DM were selected as control group. The serum concentration of OPN was detected by enzyme-linked immunosorbent assay(ELISA). Results Compared with control group, serum concentration of OPN was lower in T2DM patients;with a rising level of UACR, serum OPN declined gradually and serum OPN was the lowest in renal function impairment group(P<0.05). Pearson's analysis showed that OPN concentration was correlated negatively with UACR and serum creatinine(Scr) and positively with estimated glomerular filtration rate(eGFR, P<0.05). Univariate and multivariate Logistic regression analysis showed that duration of diabetes, fasting blood glucose, UACR, eGFR, Scr and OPN were closely correlated with progression of DN and renal function(P<005). Receiver operating curve(ROC) analysis showed that the area under the curve(AUC) of OPN concentration for diagnosing DN progression and renal function were 0.812 and 0.866 respectively(P<0.05). Conclusion In DN patients, a decline of serum osteopontin concentration is associated with disease progression and renal function injury. It is expected to become an important biochemical parameter for early assessment of disease severity.