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The endothelium lining blood and lymphatic vessels is a key barrier separating body fluids from host tissues and is a major target of <jats:italic>T.\u2009pallidum<\/jats:italic>. In this review, we focus on how <jats:italic>T.\u2009pallidum<\/jats:italic> establish intimate interactions with ECs, triggering endothelial dysfunction such as endothelial inflammation, abnormal repairment and damage of ECs. In addition, we summarize that migration and invasion of <jats:italic>T.\u2009pallidum<\/jats:italic> across vascular ECs may occur through two pathways. These two mechanisms of transendothelial migration are paracellular and cholesterol\u2010dependent, respectively. 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