Objective To investigate the relationship of serum miR-133b level with renal injury and prognosis in the elderly with diabetic nephropathy (DN). Methods A total of 182 elderly DN patients (DN group) admitted to our hospital from January 2016 to December 2017 were enrolled in this study, and another 80 matched healthy individuals taking physical examination during the same period served as control group. Real-time quantitative PCR (qRT-PCR) was used to detect serum miR-133b level, and the results were analyzed for the relationship with clinical indices in the elderly DN patients. Renal injury was evaluated by nephrotic grade, interstitial fibrosis and tubular atrophy (IFTA) score and interstitial inflammation, and the diversity of miR-133b level in different severity grades was analyzed. After the DN patients were divided into low- and high-expressed miR-133b groups, and the relationship of miR-133b level with pronostic in the two groups was also analyzed. SPSS statistics 19.0 was used to perform the statistical analysis. One-way analysis of variance, group t test, or Chi-square test was employed for intergroup comparison based on different data types. Pearson correlation analysis was performed for the correlations. Results The serum miR-133b level was significantly higher in the DN group than in the control group [(5.38±1.28) vs (1.06±0.25), P<0.01]. Significant differences were also seen in its serum level among the patients with different course of diabetes, proteinuria, serum creatinine (SCr), blood urea nitrogen (BUN) and estimated glomerularfiltration rate (eGFR) (P<0.05), and so were in those with different nephrotic grades, IFTA score and interstitial inflammation (P<0.05). What′s more, with the severity of renal pathological damage, the serum level was elevated (P<0.05). Pearson correlation analysis showed that the serum miR-133b level was positively correlated with proteinuria, SCr and BUN levels, nephrotic grade, IFTA score, and interstitial inflammation (r=0.492, 0.382,0.415,0.463,0.338,0.547, P<0.01), but negatively correlated with eGFR level (r=-0.625, P<0.01). Among the 182 elderly DN patients, 76 developed into end-stage renal disease (ESRD), with 65.9%(58/88) from the high miR-133b expression group while 19.1%(18/94) from the low expression group, indicating the former group having higher risk of ESRD (χ²=6.175, P=0.006). Conclusion Serum miR-133b level is significantly elevated, and associated with renal injury and poor prognosis in the elderly DN patients. The higher the level is, the severer the renal injury is and the poorer the prognosis is.