Abstract: Objective　To investigate the relationship between the serum expression of high mobility group protein A2 (HMGA2) and the decreased renal function in patient with diabetic nephropathy (DN). Methods　A total of 159 DN patients who were diagnosed by renal biopsy in our hospital were selected. According to the decline in renal function, DN patients were divided into rapid renal function decline group (61 cases) and non-rapid renal function decline group (98 cases). The results of laboratory examination and the expression level of serum HMGA2 were compared between the two groups, and its correlation with clinicopathological data was analyzed. Logistic regression analysis was used to explore the risk factors of renal function decline in DN patients. Receiver operating characteristic curve (ROC) was used to evaluate the diagnostic value of serum HMGA2 level in the renal function decline of DN. Results　The systolic blood pressure, serum creatinine, urea nitrogen, 24 h urinary protein, serum uric acid, HMGA2 levels, interstitial tubule scores and vascular scores were higher in the rapid renal function decline group than those in the non-rapid renal function decline group. The glomerular filtration rate (eGFR) and serum albumin level were lower in the rapid renal function decline group than those of non-rapid renal function decline group (all P＜0.05). The serum HMGA2 levels were positively correlated with serum creatinine (r=0.464) in DN patients, urea nitrogen (r=0.323), 24 h urinary protein (r=0.261), interstitial tubule score and vascular score (r=0.497), and negatively correlated with EGFR (r=-0.344) and hemoglobin (r=-0.199), (P＜0.05). The advanced age, high level of serum creatinine, 24 h urinary protein, HMGA2, low level of eGFR and serum albumin were independent risk factors for renal function decline in DN patients. HMGA2 showed a high evaluation value for renal function decline, and ROC-curve AUC was 0.760 (95% CI:0.663-0.872). The cutoff value was 1.5 μg/L, the sensitivity and specificity were 0.772 and 0.745 respectively. Conclusion　The level of serum HMGA2 expressionis increased in DN patients with renal function decline, which is closely related to the baseline renal function and the degree of tubulointerstitial and vascular lesions.