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Objective: MicroRNAs (miRNAs) regulate gene expression and are involved in diabetic kidney disease (DKD) pathogenesis. We investigated circulating miRNA-194 levels as a biomarker of DKD prevalence and incidence, and the relationship between miRNA-194 and CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP). Methods: We recruited 136 type-2 diabetes mellitus (T2DM) patients at the First People’s Hospital of Lianyungang and 127 healthy individuals. Circulating miRNA-194 and CHOP levels were measured using quantitative reverse transcription qRT-PCR and enzyme-linked immunosorbent assay (ELISA), respectively. Anthropometric and biochemistry measurements were also made. Results: T2DM patients showed higher circulating miRNA-194 ( p  = 0.029) and lower circulating CHOP ( p  < 0.001) levels than controls. Circulating miRNA-194 levels were significantly higher in T2DM patients with a microalbumin/creatinine ratio (UmALB/Cr) ⩾ 300 mg/g ( p  < 0.001). In addition, there were significant intergroup differences in the circulating CHOP concentrations ( p  = 0.005). Bivariate analysis revealed that circulating miR-194 levels were negatively correlated with alpha-fetoprotein and CHOP levels ( r  = −0.222, −0.301; p  = 0.018, 0.001, respectively), but positively correlated with fasting glucose, UmALB/Cr, Cr, Cystatin C, quantitative insulin check index (QUICKI) ( r  = 0.193, 0.446, 0.260, 0.339, and 0.250, respectively; p  = 0.036, <0.001, 0.005, <0.001, and 0.006, respectively), particularly UmALB/Cr and Cystatin C ( p  < 0.001). Logistic regression analysis after adjusting for covariates associated with UmALB/Cr identified duration of T2DM, systolic blood pressure, Cr, estimated glomerular filtration rate, and waist circumference as independent factors associated with T2DM patients with UmALB/Cr > 300 ( p  = 0.030, 0.013, <0.001, <0.001, and 0.031, respectively). Conclusion: Circulating miRNA-194 levels could be a novel biomarker for DKD.