MicroRNAs (miRNAs) are small noncoding endogenous RNA that consists approximately 19–25 nucleotides in length (Kaeuferle et al. 2014). They play a significant role by post-transcriptionally regulating the gene expression in plants and animals (Bartel, 2004; Chekulaeva and Filipowicz, 2009). Furthermore, miRNA can influence target mRNA by binding to protein-coding regions, thereby modulating the stability or translation of mRNA(1) miRNAsP1 affect a variety of key biological processes such as cell differentiation, proliferation and apoptosis, development, immunity, metabolism and stem cell maintenance (2). Therefore, function of miRNAs has provided potential pathways in various areas, such as therapeutic intervention of miRNA against pathogens has led to conduct studies related to investigate miRNA based therapy (MicroRNA therapeutics: Discovering novel targets and developing specific therapy). P2 As well different approaches have led to identify the effective use of miRNA profiling for diverse applications in disease diagnosis (MicroRNA profiling: approaches and considerations).P3 It is noted that aberrant miRNA levels can cause diseases such as cancer, age-related diseases, neurological disorders and immune function disorders. Consequently, appropriate regulation of miRNA is essential for disease prevention (3). Moreover, miRNAs have pivotal roles in eukaryotic defense mechanism of the host against extracellular, invasive bacterial pathogens and viruses (4). (5). The importance of miRNA in bacterial infections was initially discovered with the aid of miR-393, regulates auxin signaling P4 against a extracellular pathogen Pseudomonas in Arabidopsis thaliana plant. According to this discovery of miRNAs host defence function in plants, latterly miRNAs were implicated in bacterial infections in mammalians (6,7). However, immune regulations of miRNAs and characterization of miRNAs has not been studied extensively in teleost fish when compared with mammals. In 8 teleost species from five orders, 1,250 miRNAs were identified (Table 1). However, some specific miRNA genes are available only in teleost fish but not in higher vertebrates, such as miRNA-734 and miRNA-7132 P5 (Yang et al., 2015; Yan et al., 2012; Andreassen et al., 2013). Therefore, studies have conducted on identifying the miRNAs that are differentially expressed between controls and challenged groups in teleost fish. According to those reports, altered expression levels of miRNAs was observed in viral as well as bacterial infections in several teleost fish. Moreover, miRNAs contribute as regulators of Toll-like P6 receptors (tl) and following stimulation of nuclear factor (NF-kB ) signaling in bacterial infections. It is noted miRNAs responding to infection depends on the target gene(s) they regulate and many of the targets are genes from the host’s immune response gene networks (8).Aquaculture fish industry often suffers with severe infections caused by viruses, bacteria and parasites. Aeromonas hydrophila is also such bacterium; gram-negative, motile, rod-shaped which can cause motile aeromonas septicaemia (MAS) disease in fish that leads to high mortility (9, Harikrishnan and Balasundarama, 2005). Therefore, studying the immunity and host defence mechanisms of host by proper regulation of miRNA will support the control and prevention of infectious aeromonas septicaemia (MAS) disease in aquaculture industry. Zebra fish is suitable animal model for drug screening and many applications because of easy handling, fecundity and due to low cost screening (Pardo-Martin et al., 2013; Huiting et al., 2015; MacRae and Peterson, 2015; Ordas et al., 2015). The current study has been carried out using a control and challenged groups to screen miRNAs in zebrafish (Danio rerio) gut after an infection of Aeromonas hydrophila and state those identified miRNAs directly regulate the anti-bacterial activity of zebra fish.