**Abstract**

Enhanced physical activity and cardiorespiratory fitness significantly impact morbidity and mortality across the spectrum of noncommunicative chronic illnesses experienced by modern lifestyles. Physical activity itself prompts an intricate interplay of physiological responses across vital organ systems including microvascular adaptations to optimize nutrient, oxygen, and hormone delivery, some of which involves insulin-mediated regulation. Insulin has been known to act on the vasculature in multiple ways by its effects on endothelium and skeletal muscle blood flow. This is important to understand as it has implications for conditions associated with insulin resistance (IR) such as obesity, metabolic syndrome, prediabetes, diabetes, and polycystic ovarian syndrome among others. These conditions are associated with increased morbidity and mortality contributed by endothelial dysfunction via increased atherosclerosis, hypertension, and increased free fatty acid levels. In this chapter, we will discuss the effects of insulin on the vasculature, IR on the endothelium, and lastly, what impact physical activity may have on such processes.

**Keywords:** physical activity, insulin resistance (IR), endothelium
