Type 2 Diabetes mellitus (T2DM) is a highly prevalent chronic degenerative disease, which is indicated by insulin resistance (IR) in insulin-target tissues, and aberrant insulin secretion from pancreatic β-cells. Several common polymorphic genetic variants have been concerned in type 2 diabetes and insulin resistance, though the results of previous researches performed on different ethnic groups and populations are greatly contradicting. Two of the most common polymorphisms studied widely are the Ala54Thr variant of Fatty Acid Binding Protein 2 (FABP2) gene, and the Pro12Ala variant of Peroxisome Proliferator Activated Receptor Gamma (PPARγ) gene. A number of other non-genetic factors also significantly affect insulin resistance, like body composition, regular levels of physical exercises, gender and age. In this review, we discuss both genetic and non genetic factors, the relationship between insulin resistance and T2DM, how the polymorphisms in two candidate genes FABP2 and PPARγ affect the T2DM, IR and other diseases in different populations and ethnic groups.