Abdominal aortic aneurysm (AAA) is a chronic and severe aortic disease. Our previous studies have indicated that monocyte chemotactic protein-induced protein-1 (MCPIP1) is involved in AAA. However, the exact effect of MCPIP1 on angiotensin II (Ang II)-induced AAA formation is currently unknown. MCPIP1 deficiency reduced AAA formation in Ang II-induced mice. Less collagen and elastin degradation were observed in MCPIP1-deficient mice treated with Ang II. Ang II decreased αSMA and SM22α levels in aortas and vascular smooth muscle cells (VSMCs), whereas MCPIP1 deficiency reduced this decrease. MCPIP1 deficiency also attenuated Ang II-induced expression of MAPK signaling-associated proteins in aortas and VSMCs. Silencing MCPIP1 decreased proliferation and migration in Ang II-induced VSMCs. Furthermore, inactivation of ERK1/2 with PD98059 reduced Ang II-induced proliferation and migration of VSMCs. Dual luciferase and chromatin immunoprecipitation assay results confirmed that MCPIP1 was transcriptionally regulated by KLF4. KLF4 knockdown reversed the facilitating effect of Ang II on MCPIP1 expression. In conclusion, our findings suggest that MCPIP1 promotes Ang II-induced VSMCs phenotypic switching via the MAPK signaling pathway.