Abstract: Objective To detect differentially expressed microRNA（miRNA） in urine exosomes of metabolic syndrome（MS） patients with renal damage, and to explore the role of miRNAs in the pathogenesis of renal damage in MS. Methods The patients who were diagnosed with MS renal damage and MS without renal damage at the 900th Hospital of Joint Logistic Support Force, PLA from May 2018 to December 2019, as well as the health examinations were selected. Real-time quantitative polymerase chain reaction（PCR） and high-throughput sequencing were used to detect the expression of urinary exosomal miRNAs in MS renal damage patients（MS renal damage group, n=3） and health examinations（control group, n=3）. Bioinformatics analysis of differentially expressed miRNAs was performed to explore the main biological functions of the target genes. The differentially expressed miRNAs and their target genes were verified in 14 MS patients with renal damage, 14 MS patients without renal damage, and 14 health examinations. Results High-throughput sequencing analysis showed that 33 differentially expressed miRNAs in urinary exosome were present between the MS renal damage group and the control group（P＜0.05）. Real-time quantitative PCR with a small sample size showed that there were 11 differentially expressed miRNAs（P＜0.05）, among which 7 were up-regulated（miRNA-449a, miRNA-449b-5p, miRNA-449c-5p, miRNA-122-3p, miRNA-618, miRNA-217-5p, miRNA-2115-3p）, 4 were down-regulated（miRNA-4662a-5p, miRNA-1-3p, miRNA-3114-3p, miRNA-95-3p）. Then miRNA-449a was selected for further clinical validation due to its significant difference and stable expression（P＜0.05）. Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analysis showed that target genes of differentially expressed miRNA may participate in the progression of MS renal damage through mitogen-activated protein kinase（MAPK） signal pathway, transforming growth factor β（TGF-β） signal pathway, Wnt signal pathway and other pathway. MiRNA-449a in urine exosomes was significantly different among MS renal damage group, MS without renal damage group and control group（0.70±0.32 vs 0.42±0.28 vs 0.06±0.06, F=26.062, P＜0.001）, and the expression of miRNA-449a in patients with MS renal damage was significantly up-regulated. The expression of miR-449a in patients with MS renal damage was positively correlated with serum creatinine and urinary microalbumin to creatinine ratio（P＜0.05）. The expression of Bcl-2 mRNA（downstream target gene of miRNA-449a） in MS patients with renal damage was significantly down-regulated comparing to MS patients without renal damage（0.02±0.01 vs 0.06±0.01, t=102.756, P＜0.001）. Conclusions There are differentially expressed miRNAs in urinary exosomal of MS patients with renal damage. Bioinformatics analysis suggests that genes such as differentially expressed Bcl-2 mRNA may be involved in the development and progression of renal damage in MS.