INTRODUCTION: Inflammation is a major determinant of abdominal aortic aneurysms (AAA). Interferon stimulated gene 15 (ISG15) has a role in vascular remodelling in AAA. This study investigates the mechanisms whereby ISG15 might affect vascular remodeling and function. METHODS: We used vascular smooth muscle cells (VSMC) from wild type (ISG15 RESULTS: In VSMC, ISG15 deficiency increased the expression of contractile (Acta2, Tagln) and synthetic (Fn1, Col1a2, Col3, Col4) markers and decreased the expression of the calcification marker Spp1. Ang II infusion changed the expression of phenotype markers differently in aorta from ISG15 CONCLUSIONS: ISG15 participates in pathological vascular remodeling probably by modulating VSMC phenotype. These changes could also impact in the vascular function.