Abstract Metabolic syndrome greatly increases the risk for developing metabolic and cardiovascular disorders and has reached epidemic proportions globally. Despite recent advances in medical science, scientific understandings on the root mechanisms of metabolic syndrome are still not fully understood, and such insufficient knowledge contributes to the relative lack of effective treatments for such diseases. Protein Kinase R (PKR) is a serine threonine kinase activated during various stress conditions. Activation of PKR can increase reactive oxygen product generation, cause oxidative stress and inflammation. In this review we discuss the potential role of PKR in metabolic syndrome, pathways activated by it and the interrelationship between pathways activated, modes of propagation if one of the pathways is inhibited or activated. Specific and effective inhibitors of PKR are being developed and can become potential treatment for metabolic syndrome and prevent many diseases.