Since the discovery of the stability of extracellular microRNAs (miRNAs) in plasma and other body fluids about a decade ago, an increasing body of literature has addressed the function of extracellular miRNAs as novel regulators of gene expression. Although many of these studies have demonstrated that extracellular miRNAs modulate the target genes of recipient cells in a conventional base-pairing manner after exosome-mediated secretion and uptake of miRNAs, recent studies have shown that extracellular miRNAs can also play an unconventional role by rapidly modulating innate immunity and neuron excitation via directly binding to Toll-like receptors (TLRs). In this review, we will summarize the literature incremented from studying the direct activation of TLR signaling pathways by miRNAs and miRNA-like fragments in modulating immune responses. Keywords: Extracellular microRNAs, Immunostimulation, Toll-like receptor