The transplantation of mesenchymal stem cells (MSCs) has been a reported method for alleviating atherosclerosis (AS). Because the availability of bone marrow‑derived MSCs (BM‑MSCs) is limited, the authors used this study to explore the use of a new type of MSC, human induced pluripotent stem cell‑derived MSCs (iPSC‑MSCs), to evaluate whether these cells could alleviate AS. iPSC‑MSCs were intravenously administered to ApoE knock out mice fed on a high‑fat diet (HFD) for 12 weeks. It was reported that systematically administering iPSC‑MSCs clearly reduced the size of plaques. In addition, the numbers of macrophages and lipids in plaques were lower in the HFD + iPSC‑MSCs group than in the HFD group. Furthermore, iPSC‑MSCs attenuated AS‑associated inflammation by decreasing the levels of inflammatory cytokines, such as tumor necrosis factor‑α and interleukin‑6, in serum. In addition, the expression of Notch1 was higher in the HFD group, and injecting iPSC‑MSCs reversed this effect. In conclusion, the current study provides the first evidence indicating that iPSC‑MSCs may be a new optional MSC‑based strategy for treating AS.