Diabetes mellitus is a group of metabolic diseases. Insulin resistance is defined as a state that needs more insulin to get the biological effects achieved by a lower amount of insulin in the normal state. Several molecules which are secreted through adipocytes have been involved in insulin resistance and type 2 diabetes mellitus. Adiponectin as a 244 amino acid protein is exclusively expressed in differentiated adipocytes. Recent studies indicated impaired multimerization of adiponectin is associated with type 2 diabetes development. Moreover, the relationship between adiponectin, insulin and insulin resistance is not known and many mechanisms have been proposed. Inverse relationship between adiponectin and insulin resistance may be mediated through insulin and other hormones like catecholamines or androgens. Moreover, intensive insulin treatment increased serum C-peptide and adiponectin level resulted to improving sensitivity of insulin and decreased CRP level. According to these studies, it seems that adiponectin may be an important modulator of insulin action for enhancing of sensitivity of insulin.