Abdominal aortic aneurysm (AAA) is a lethal disease without available medicine for treatment. This study aimed to evaluate the efficiency of eugenol (4-allyl-2-methoxyphenol) against AAA and the underlying mechanism. Eugenol is the major bioactive component of clove. A mouse AAA model was established through porcine pancreatic elastase (PPE) incubation peri-adventitially and 1% 3-aminopropanonitrile (BAPN) diet. Continuous AAA progression from day 0 to day 15 was observed after PPE plus BAPN treatment, according to the AAA diameter and histopathological evaluation. Accompanying with AAA progression, sustained increased expressions of CD68, COX-2 and NF-κB were observed through immunofluorescence assay. After elucidation the efficiency of eugenol against AAA progression by AAA diameter, hematoxylin-eosin staining and orcein staining, the down-regulations of eugenol on COX-2 and NF-κB were further detected by immunohistochemistry and western blot. Eugenol not only blocked AAA expansion and protected the integrity of aortic structure in a dose-dependent manner, but also held high oral bioavailability. Excellent efficiency, high oral bioavailability and down-regulation on COX-2/NF-κB endowed eugenol great potential for future AAA therapy.