Aim To investigate the correlation between circulating microRNA-204 levels and coronary CT angiography (CTA) calcification score(CACS) in patients with diabetes. Methods Clinical data from 179 patients diagnosed with diabetes who underwent coronary CT angiography in our hospital from January 2017 to December 2018, were cross-section analyzed. Patients were divided into moderate to severe calcification group(CACS＞0,9 cases) and non-or minimal calcification group (CACS≤0,0 cases). Five patients with coronary artery calcification (CAC) (CACS＞10) and 5 patients with non-CAC (CACS≤10) were selected for microRNA microarray analysis of plasma microRNAs. Two groups of microRNA-204 were quantified by using qRT-PCR and univariate linear regression was performed to assess the potential correlation between microRNA-204 levels and CACS. The potential diagnostic ability of microRNA-204 was assessed by ROC curve analysis. Results There was significant difference in fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c) between two groups (P＜0.05). MicroRNA microarray analysis showed a significant decrease in microRNA-204 expression levels in the CAC group compared with the non-CAC group. MicroRNA-204 was significantly down-regulated in the moderate-to-severe calcification group by qRT-PCR (P＜0.05). Univariate linear regression analysis showed that circulating microRNA-204 levels in moderate to severe calcification group were negatively correlated with CACS, which reflected the severity of coronary artery calcification. The ROC curve showed that the area under the curve of microRNA-204 levels predicting vascular calcification of patients with diabetes was 0.948 7(0.919 1～0.978 2, P＜0.0001) and the diagnostic threshold was 21.3, the sensitivity was 96.3%, the specificity was 79.6%. Conclusion The expression level of microRNA-204 in plasma of CAC patients decreased significantly, but there was a negative correlation between the severity of CAC and microRNA-204, which may be of great significance to further verify that the level of microRNA-204 in human plasma macroscopically reflects the severity of CAC in patients with diabetes mellitus. MicroRNA-204 may be a new biomarker for the diagnosis of coronary artery calcification.