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This study aimed to investigate the correlation between serum miR-154-5p and urinary albumin to creatinine ratio (UACR) in patients with type 2 diabetes mellitus (T2DM) and the association with biomarkers of inflammation and fibrosis in diabetic kidney disease (DKD).A total of 390 patients with T2DM were divided into three groups: normal albuminuria (UACR ＜ 30 mg/g,n =136,NA),microalbuminuria (UACR at 30-300 mg/g,n =132,MA),and clinical albuminuria (UACR ＞ 300 mg/g,n =122,CA).Circulating miR-154-5p,inflammatory (C-reactive protein (CRP);erythrocyte sedimentation rate (ESR);and tumor necrosis factor-α (TNF-α) and fibrotic markers (vascular endothelial growth factor (VEGF);transforming growth factor-β1 (TGF-β1);and fibronectin (FN)),and other biochemical indicators were assessed via real-time PCR,enzyme-linked immunosorbent assay,and chemiluminescence assay in patients with T2DM and 138 control subjects (NC).UACR,miR-154-5p,glycated hemoglobin (HbA1c),serum creatinine (sCr),blood urea nitrogen (BUN),ESR,CRP,VEGF,TNF-α,TGF-β1,and FN were significantly higher and the estimated glomerular filtration rate (eGFR) was significantly lower in NA,MA,and CA groups than in NC subjects (P ＜ 0.05).Elevated levels of UACR and miR-154-5p were directly correlated with HbA1c,sCr,BUN,ESR,CRP,VEGF,TNF-α,TGF-β1,and FN and negatively correlated with eGFR (P ＜ 0.05).miR-154-5p,HbA1c,sCr,BUN,eGFR,ESR,CRP,VEGF,TNF-α,TGF-β1,and FN were important factors affecting UACR.These findings indicated that elevated serum miR-154-5p is significantly correlated with high UACR in patients with T2DM and may offer a novel reference for the early diagnosis of DKD.