Background: Apelin is a potent inodilator with recently described antiatherogenic properties. We hypothesized that apelin might also attenuate AAA formation by limiting disease-related vascular wall inflammation. Methods and Results: C57BL/6 mice implanted with osmotic pumps filled with apelin or saline were treated with pancreatic elastase to create infrarenal AAA's. Mice were sacrificed for aortic PCR analysis or followed ultrasonographically and then sacrificed for histological analysis. The cellular expression of inflammatory cytokines and chemokines in response to apelin was also assessed in cultured macrophages, smooth muscle cells, and fibroblasts. Apelin treatment resulted in diminished AAA formation, with a 47% reduction in maximal cross-sectional area (0.74 mm² vs 1.39 mm², P < 0.03) and a 57% reduction in macrophage infiltrate (113 cells/hpf vs 261.3 cells/hpf, P <0.0001) relative to the saline-treated group. Apelin infusion was also associated with significantly reduced aortic MCSF expression, and decreased MCP-1, MIP 1-, IL-6 and TNF- mean mRNA levels. Apelin stimulation of cultured macrophages significantly reduced MCP-1 and TNF- mRNA levels relative to baseline (2.03 and 1.89 fold reduction, P < 0.03, respectively) but did not affect intimal adhesion molecule expression or medial or adventitial cell cytokine production. Conclusions: Apelin significantly reduces aneurysm formation in the elastase model of human AAA disease. The mechanism appears to be decreased macrophage burden, perhaps related to an apelin-mediated decrease in pro-inflammatory cytokine and chemokine activation.