MicroRNA (miR)-22-3p is expressed in atherosclerosis (AS), but its function and regulatory mechanisms remain unclear. Therefore, the effects of miR-22-3p in AS were assessed in this study.MiR-22-3p expression was assessed in AS, and miR-22-3p target genes were predicted using sequencing transcriptomics. The effect of miR-22-3p agomir on atherosclerotic lesions in an AS mouse model were determined by Oil red O, Masson's, and sirius red staining, and by anti-smooth muscle actin and macrophage antigen-3 immunostaining. Gene expression in AS was evaluated by western blot and immunofluorescence.MiR-22-3p was expressed in AS and control samples (32.5% and 33.9% levels, respectively, relative to total miRNA among six highly expressed miRNAs). In the mouse model of AS, miR-22-3p agomir significantly reduced lipid deposition, proliferation of aortic collagen fibres, and macrophage content. Additionally, inducible nitric oxide synthase, interleukin-6, and tumour necrosis factor-α levels were significantly reduced, and levels of arginase 1 and CD206 were significantly enhanced. MiR-22-3p was found to target janus kinase 1(JAK1), and significantly inhibited the activation of NLR family pyrin domain containing 3 (NLRP3) and JAK1 in mice.MiR-22-3p appears to reduce the inflammatory response in AS, which might be achieved by inducing the M2 macrophage phenotype and suppressing NLRP3 activation via JAK1.