Atherosclerosis is a chronic inflammatory disease, and it is a global clinical problem. The development of new and effective therapeutic targets for atherosclerosis is necessary. A number of microRNAs (miRNAs) have been demonstrated to serve a crucial role in atherosclerosis. However, the role of miRNA (miR)?217 in atherosclerosis remains unclear. Therefore, the aim of the present study was to investigate the role and mechanism of miR?217 in atherosclerosis. The level of miR?217 was detected in the blood of patients with atherosclerosis using reverse transcription?quantitative PCR. THP?1 acute monocytic leukemia cells were treated with oxidized low?density lipoprotein (ox?LDL) to develop an atherosclerotic cell model of macrophages. The relationship between miR?217 and sirtuin 1 (SIRT1) was determined by TargetScan and dual luciferase reporter assay. Cell apoptosis was measured by flow cytometry. Production of pro?inflammatory factors and triglyceride (TG) and total cholesterol (TC) levels were also determined. The results demonstrated that miR?217 was significantly upregulated in atherosclerosis. SIRT1 was demonstrated to be a direct target of miR?217 and was downregulated in atherosclerosis. Downregulation of miR?217 significantly inhibited ox?LDL?induced TG and TC level increase, cell apoptosis and the upregulation of the pro?inflammatory factors tumor necrosis factor α, interleukin (IL)?6 and IL?1β. Additionally, the SIRT1/AMP?activated protein kinase α/NF?κB pathway was at least partially involved in modulating the effects of miR?217 inhibition on THP?1 cells treated with ox?LDL. In addition, the effects of miR?217 downregulation on ox?LDL?treated THP?1 cells were eliminated by SIRT1 silencing. In conclusion, the results of the present study indicated that miR?217 downregulation may relieve atherosclerosis through the inhibition of macrophage apoptosis and inflammatory response by targeting SIRT1.