In horses, insulin resistance is associated with several comorbidities such as obesity, laminitis, colic and osteochondrosis. The multifactorial causes of insulin resistance in horses have been addressed, which include genetic and environmental factors. As a consequence of these factors, the cellular signaling pathways responsible for insulin synthesis, the glucose intake in target cells of peripheral tissues and other related processes (e.g., adipocytokine signaling pathways) are affected. In response to insulin, changes in gene expression occur, which are required for the integration of an entire network of metabolic and physiological responses in different organs. The peroxisome proliferator-activated receptors (PPARs) were the particular focus of studies in recent years, mostly in humans. The PPARs are the primary transcriptional regulators of adipocyte differentiation and lipid metabolism. They have a direct effect on the expression of the genes involved in glucid homeostasis and were recently associated with type-2 diabetes. A molecular framework to define the insulinrelated pathologies has not been developed for horses. Additionally, the establishment of a proper diagnosis of insulin resistance is fundamental in this species. The aims of this review were to discuss the etiology to identify the primary causes of insulin resistance and to examine the current progress in understanding this pathology in horses. Future research should study how nutrients modulate the expression of genes related to energy metabolism under the physiopathological condition of insulin resistance.