The aim of the study was to determine whether the release by macrophages of matrix metalloproteinase (MMP)-12 and vascular endothelial growth factor (VEGF)-leading to inflammation, matrix degradation and neoangiogenesis-represents an effective pathway that underlies aortic wall remodeling in Stanford type A acute aortic dissection (AAD). Twenty-one consecutive patients with no genetic predisposition, with Stanford type A AAD were selected. In each patient, the levels of serum VEGF, MMP-12, serum interleukin (IL)-6, IL-8 and monocyte chemoattractant protein (MCP)-1 were evaluated using enzyme-linked immunosorbent assay. Ascending aortic specimens were collected for immunohistochemical identification of any presence of inflammatory infiltrate, VEGF and CD31 expression. A significant increase in serum VEGF (p= 0.044), MMP-12 (p= 0.007), IL-6 (p= 0.0001), IL-8 (p= 0.0001) and MCP-1 (p= 0.0001) levels was observed in the AAD group compared to the control group. Furthermore, all AAD samples were positive for VEGF in the tunica media and showed vessel growth and immune-inflammatory infiltrate. A large number of cases (62.79%) showed inflammation at the edge of the dissection and approximately half (51.42%) showed neovessels growing at the edge of the dissection. The results suggest that VEGF-mediated angiogenesis and matrix degradation play a role in AAD. Finally, we believe that MMP-12 should be considered a marker of AAD.