Diabetic vasculopathy refers to diabetes-induced microvascular and macrovascular complications, including retinopathy, neuropathy, atherosclerosis, coronary artery disease, hypertension, and peripheral artery disease. Hyperglycemia and insulin resistance/hyperinsulinemia contribute to cardiometabolic syndrome and predispose to diabetic vasculopathy. The underlying mechanisms include inappropriate activation of the renin-angiotensin-aldosterone system, mitochondrial dysfunction, oxidative stress, inflammation, dyslipidemia, and thrombosis. Recent evidence also highlights the role of endothelial progenitor cell dysfunction, gut dysbiosis, and abnormal extracellular vesicle release in the development of diabetic vasculopathy. Clinical control of diabetes and novel therapeutic strategies are crucial for preventing cardiometabolic syndrome and related vascular complications. This review discusses the relationship between insulin resistance and diabetes in diabetic vasculopathy and related cardiovascular disease, highlighting epidemiology, clinical characteristics, pathophysiology, molecular mechanisms, and management strategies. Diabetic vasculopathy is associated with cardiovascular disease, including atherosclerosis, coronary artery disease, hypertension, and peripheral artery disease. Hyperglycemia and insulin resistance/hyperinsulinemia increase the prevalence of diabetic vasculopathy and related cardiovascular disease. Mechanistically, inappropriate RAAS activation, mitochondrial dysfunction, oxidative stress, inflammation, dyslipidemia, thrombosis, endothelial progenitor cell dysfunction, gut dysbiosis, and abnormal extracellular vesicle release contribute to the development and progression of diabetic vasculopathy. Therapeutic strategies including lifestyle changes, glycemic control, antithrombotic therapy, lipid-lowering, and antihypertensive treatments are beneficial in preventing diabetic vasculopathy. Intensive application of these therapies has significantly reduced cardiovascular events and total mortality. However, the risk of adverse cardiovascular outcomes remains higher in individuals with diabetes. Understanding the pathophysiology of insulin resistance and diabetes mellitus and associated vascular complications will facilitate the development of novel treatments for diabetic vasculopathy.Diabetic vasculopathy refers to diabetes-induced microvascular and macrovascular complications, including retinopathy, neuropathy, atherosclerosis, coronary artery disease, hypertension, and peripheral artery disease. Hyperglycemia and insulin resistance/hyperinsulinemia contribute to cardiometabolic syndrome and predispose to diabetic vasculopathy. The underlying mechanisms include inappropriate activation of the renin-angiotensin-aldosterone system, mitochondrial dysfunction, oxidative stress, inflammation, dyslipidemia, and thrombosis. Recent evidence also highlights the role of endothelial progenitor cell dysfunction, gut dysbiosis, and abnormal extracellular vesicle release in the development of diabetic vasculopathy. Clinical control of diabetes and novel therapeutic strategies are crucial for preventing cardiometabolic syndrome and related vascular complications. This review discusses the relationship between insulin resistance and diabetes in diabetic vasculopathy and related cardiovascular disease, highlighting epidemiology, clinical characteristics, pathophysiology, molecular mechanisms, and management strategies. Diabetic vasculopathy is associated with cardiovascular disease, including atherosclerosis, coronary artery disease, hypertension, and peripheral artery disease. Hyperglycemia and insulin resistance/hyperinsulinemia increase the prevalence of diabetic vasculopathy and related cardiovascular disease. Mechanistically, inappropriate RAAS activation, mitochondrial dysfunction, oxidative stress, inflammation, dyslipidemia, thrombosis, endothelial progenitor cell dysfunction, gut dysbiosis, and abnormal extracellular vesicle release contribute to the development and progression of diabetic vasculopathy. Therapeutic strategies including lifestyle changes, glycemic control, antithrombotic therapy, lipid-lowering, and antihypertensive treatments are beneficial in preventing diabetic vasculopathy. Intensive application of these therapies has significantly reduced cardiovascular events and total mortality. However, the risk of adverse cardiovascular outcomes remains higher in individuals with diabetes. Understanding the pathophysiology of insulin resistance and diabetes mellitus and associated vascular complications will facilitate the development of novel treatments for diabetic vasculopathy.