Due to the important role of increased oxidative stress and inflammation in the pathophysiology of DM and the valuable properties of His in the inhibition of oxidative damages, glycation, and reduction of insulin resistance, this study was carried out to evaluate the effects of His on oxidative stress biomarkers, lipid profile, cardiac risk ratios, insulin, insulin resistance (HOMA-IR), renal histological alterations, and the renal gene expressions of anti-oxidant enzymes and TNF-α in Wistar rats with streptozotocin/nicotinamide (STZ/NA)-induced T2D. This evidence concerns the gene INS and type 2 diabetes mellitus.