Background Chronic inflammation plays a key role in the pathogenesis of intracranial aneurysms ( IA s). DPP‐4 (dipeptidyl peptidase‐4) inhibitors have anti‐inflammatory effects, including suppressing macrophage infiltration, in various inflammatory models. We examined whether a DPP ‐4 inhibitor, anagliptin, could suppress the growth of IA s in a rodent aneurysm model. Methods and Results IA s were surgically induced in 7‐week‐old male Sprague Dawley rats, followed by oral administration of 300 mg/kg anagliptin. We measured the morphologic parameters of aneurysms over time and their local inflammatory responses. To investigate the molecular mechanisms, we used lipopolysaccharide‐treated RAW 264.7 macrophages. In the anagliptin‐treated group, aneurysms were significantly smaller 2 to 4 weeks after IA induction. Anagliptin inhibited the accumulation of macrophages in IA s, reduced the expression of MCP‐1 (monocyte chemotactic protein 1), and suppressed the phosphorylation of p65. In lipopolysaccharide‐stimulated RAW 264.7 cells, anagliptin treatment significantly reduced the production of tumor necrosis factor α, MCP ‐1, and IL‐6 (interleukin 6) independent of GLP‐1 (glucagon‐like peptide 1), the key mediator in the antidiabetic effects of DPP ‐4 inhibitors. Notably, anagliptin activated ERK5 (extracellular signal–regulated kinase 5), which mediates the anti‐inflammatory effects of statins, in RAW 264.7 macrophages. Preadministration with an ERK 5 inhibitor blocked the inhibitory effect of anagliptin on MCP ‐1 and IL ‐6 expression. Accordingly, the ERK 5 inhibitor also counteracted the suppression of p65 phosphorylation in vitro. Conclusions A DPP ‐4 inhibitor, anagliptin, prevents the growth of IA s via its anti‐inflammatory effects on macrophages.