There is a growing body of evidence indicating that obesity and insulin resistance contribute to the progression of renal disease. A low-grade inflammatory response occurs in obesity and insulin resistance that causes an increase in macrophage infiltration into the adipose tissue and the kidney. The infiltration of macrophages gives rise to the production of an array of pro-inflammatory cytokines and downstream elements such as interleukin-6, NFkappaB, and cellular adhesion molecules. In addition, increased adiposity triggers the release of adipokines such as leptin that can cause vascular remodeling and disruption of renal function. Insulin resistance can alter the balance between endogenous vasoactive molecules such as nitric oxide and reactive oxygen species, resulting in altered renal endothelial function. Moreover, hyperinsulinemia has direct renal effects such as induced relaxation of the afferent arteriole, resulting in glomerular hyperfiltration and renal damage. High insulin levels also stimulate angiogenesis and mesangial cell proliferation, associated with the development of diabetic nephropathy. Current evidence indicates a direct link between increased adiposity and insulin resistance with renal vascular injury; however, further investigation into the renal microvascular effects of obesity and insulin resistance are required to better understand this disease process.