Insulin resistance syndrome is a major risk factor for atherosclerosis and coronary heart disease (CAD). Endothelial dysfunction due to reduced nitric oxide generation is seen in both insulin resistance syndrome and CAD. Endothelial dysfunction also occurs in obesity, diabetes mellitus, and other cardiovascular diseases. In the present study, we employed multiple sequence alignment using Clustal W tool and constructed a phylogenetic tree using functional protein sequences extracted from NCBI and Gene cards. These studies showed that nitric oxide synthase and adiponectin play a major role in insulin resistance and coronary artery disease. This and other studies suggest that endothelial dysfunction is an early event in insulin resistance syndrome.