As a versatile regulatory mechanism, sumoylation has been found to be essential for ordered diverse cellular processes. However, the exact impact of sumoylation on endothelial function largely remained elusive. Here we investigated the role of small ubiquitin-like modifier 1 (SUMO1) mediated sumoylation in the regulation of endothelial function by examining its effect on angiogenesis and homeostatic responses. Adenoviral-mediated SUMO1 expression in porcine aortic endothelial cells (PAECs) dose-dependently promoted proliferation, migration and tube formation. In line with these results in PAECs, Matrigel plug assays in SUMO1 transgenic mice demonstrated a significant higher capacity for vascular neogenesis as compared with that of control littermates. Moreover, SUMO1 expression protected PAECs from serum starvation or H2O2-induced apoptosis. Mechanistic studies demonstrated that SUMO1 sumoylation modulates ERK1/2 activation and MMP13 expression as well as Jak2/STAT5 signaling to promote angiogenesis. SUMO1 sumoylation also suppressed NF kappa B and c-JUN transcriptional activity to provide protection for PAECs against oxidative stress-induced apoptosis. Given that sumoylation is a reversible process, dynamic regulation of the sumoylation function could be a novel strategy to modulate endothelial function in disease states.