Monocyte chemotactic protein-induced protein 1 (MCPIP1) plays a crucial role in various cellular processes, including neurogenesis. However, the relationship between MCPIP1 and myocardial ischemia/reperfusion (I/R) injury remained illdefined. In this study, we explored whether the I/R-mediated up-regulation of MCPIP1 is critical in the modulation of both cell migration and apoptosis in human umbilical vein endothelial cells (HUVECs). Using Western blot analysis and quantitative real-time PCR, the protein expression and mRNA transcription, respectively, of MCPIP1 was detected in HUVECs. To investigate cell migration, an in vitro scratch assay and a nested matrix model were applied. I/R increased the expression of MCPIP1 via the activation of the mitogen-activated protein kinase (MAPK) and PI3K/Akt pathways. I/R increased migration and apoptosis of HUVECs, which were significantly inhibited by MCPIP1 siRNA. These findings suggest that I/R-mediated up-regulation of MCPIP1 regulates migration and apoptosis in HUVECs. Understanding the regulation of MCPIP1 expression and function may aid in the development of an adjunct therapeutic strategy in the treatment of individuals with I/R injury.