Abdominal aortic aneurysms (AAA) is a multifactorial vascular disease with a high rate of mortality and brings heavy burden to both human and society. The pathological process behind AAA is complex. Elastin degradation, chronic inflammation, and vascular smooth muscle cell phenotypic modulation are involved in AAA formation. Apigenin (API) has gained much attention due to its specific properties, such as anti-inflammation, antioxidant, and anti-cancer effects. Previous studies have demonstrated that API exert beneficial effects on prevention of cardiovascular diseases. However, the effects of API on AAA are still unknown. Here, we for the first time evaluated API-related effects on AAA formation using a Cacl2-induced AAA model. Compared with the AAA group, treatment with API reduced the incidence of AAA, attenuated pathological expansion of the aorta, and preserved elastic fiber in a dose-dependent manner. In addition, API attenuated vascular inflammation by inhibiting activation of matrix metalloproteinase and modulated vascular smooth muscle cell contractile phenotypic transition. The preventative effect of API on AAA might be associated with the downregulation of nuclear factor-kappa B (NF-κB) activity via the IKK-dependent signaling pathway. Our findings firstly revealed that API could suppress AAA formation in a dose-dependent manner by inhibiting the NF-κB signaling pathway, and API should be considered as a promising therapeutic drug in prevention of AAA.