Objective:　Studies　have　probed　the　function　of　microRNA　(miR)-16-5p　in　the　progression　of　atherosclerosis　(AS),　while　the　regulatory　function　of　exosomal　miR-16-5p　from　macrophage　on　AS　remains　largely　unknown.　This　study　commits　to　exploring　the　efficiency　of　exosomal　miR-16-5p　from　macrophage　on　AS　via　modulating　mothers　against　decapentaplegic　homolog　7　(SMAD7).Methods:　Macrophages　were　cultured　and　transfected　with　miR-16-5p　antagomir,　then,　the　exosomes　from　macrophages　were　extracted.　The　AS　mouse　model　was　established,　and　miR-16-5p　or　SMAD7　expression　in　AS　mice　was　detected.　Thereafter,　the　effects　of　macrophage-derived　exosomes,　miR-16-5p　or　SMAD7　on　serum　inflammatory　response,　oxidative　stress　response,　pathological　changes　and　apoptosis　in　AS　mice　were　observed　by　immunohistochemical　and　biochemical　analysis.　Finally,　the　binding　relation　between　miR-16-5p　and　SMAD7　was　examined.Results:　MiR-16-5p　was　elevated　while　SMAD7　was　depleted　in　AS　mice.　Macrophage-derived　exosomes　aggra-vated　AS　progression　via　facilitating　inflammatory　response　and　oxidative　stress,　exacerbating　pathological　changes　and　increasing　cell　apoptosis　in　AS　mice;　while　downregulation　of　miR-16-5p　reversed　the　exacerbation　of　AS　progression　by　macrophage-derived　exosomes　in　AS　mice.　MiR-16-5p　targeted　SMAD7,　and　the　down-regulated　SMAD7　reversed　the　impacts　of　depleted　miR-16-5p　on　AS　progression.Conclusion:　Exosomal　miR-16-5p　from　macrophages　aggravates　AS　progression　via　downregulating　SMAD7　expression.　This　study　provides　novel　therapeutic　targets　for　AS　treatment　from　the　animal　level.