Therefore, we attempted to explore the PKR inhibitory property of IHZ in high fructose (HF) and streptozotocin (STZ) induced T2D animal model16 and are here for the first time reporting the therapeutic potential of IHZ in attenuating PKR mediated disruption of lipid and glucose homeostasis via downregulation of inflammatory cascade. This evidence concerns the gene EIF2AK2 and type 2 diabetes mellitus.