Restenosis is a pathologic re-narrowing of a coronary artery lesion after mechanical injury. Its pathophysiological mechanisms have not been fully elucidated at present, but are thought to include inflammation, vascular smooth muscle cell (VSMC) proliferation, and matrix remodeling, beginning with insufficient endothelium healing. Restenosis presents with angina symptoms or acute coronary syndromes and lead to a revascularization, either with coronary artery bypass or repeat percutaneous coronary intervention. Some studies have reported that hypoadiponectinemia has been an independent risk factor for the onset of acute coronary syndromes and restenosis. Accumulating evidence shows that low concentrations of adiponectin may be involved in impairing endothelium functions, inflammation, and VSMC proliferation that lead to restenosis. Preclinical studies have proven that adiponectin promotes endothelium healing, effectively inhibits inflammation, and maintains contractile phenotypes of VSMCs, indicating that it may be developed as a new therapeutic target for the treatment of restenosis.