Circulating miRNAs have received extensive attention as non-invasive biomarkers for prediction and diagnosis of disease. However, most samples have been obtained from peripheral venous blood. To evaluate whether peripheral venous miRNAs represent circulating miRNAs from all blood vessels under a given condition, such as aging, we compared the miRNA profiles of venous and arterial plasma between young and aged rats by Illumina next-generation sequencing. The DEseq2 tool was used to obtain differentially-expressed miRNAs. We observed 105 aging-related deregulated miRNAs in vein and 62 in artery, which were highly associated with cell survival and inflammation, respectively. On the other hand, the young and aged groups exhibited a unique arterial-venous bias. There were 54 differentially-expressed miRNAs in the young group and 42 in the aged group; only 8 miRNAs were shared. Further transcriptional factors enrichment analysis found that the shared miRNAs could be partially upregulated by NF-κB and SIRT1. These transcriptional factors could be organ-specific and/or regulated in physiological and aging states as possible causal factors. This study suggested the potential application of circulating miRNAs, which reflect the systematic response to certain conditions, such as aging, and the importance of origin selection for candidate circulating miRNAs.