OBJECTIVE To investigated the role of Mailuoning in the prevention of high-glucose-mediated cell apoptosis in human umbilical vein endothelial cells (HUVEC) and the mechanisms involved. METHODS MTT assay was used to investigate cell viability, western blot was used to investigate protein expression, and flow cytometric detection technology was used to detect cell apoptosis. RESULTS Exposure of HUVEC to high glucose (50 mM) significantly suppressed cell viability and increased cell apoptosis compared with normal glucose (11 mM) (all P < 0.05). However, Mailuoning prevented high-glucose-induced HUVEC apoptosis in dose-dependent manner. Further studies indicated that Mailuoning suppressed high-glucose-induced p38 mitogen-activated protein kinase phosphorylation, but had no effect on extracellular signal-regulated kinase 1/2 and Akt phosphorylation. CONCLUSION Mailuoning can prevent high-glucose-induced HUVEC apoptosis by suppressing p38 activation.