High levels of miR-23a expression in human primary macrophages suggested that miR-23a might have an important role in innate immune cells. Therefore, we investigated whether miR-23a regulates the secretion of cytokines by immune cells. Herein, we demonstrate that the expression of miR-23a was reduced in toll-like receptor (TLR)-stimulated macrophages. By targeting A20, miR-23a could affect NF-kappaB activity and the expression of downstream NF-kappaB-target genes that encode proinflammatory mediators, such as IL-6 and TNF-alpha. In summary, our study describes a novel role for miR-23a in the regulation of inflammatory cytokine production in macrophages, which could yield new insights into the regulatory role of miRNAs in the inflammatory response.