The hyperglycemic phenotype of diabetic KK-Ay mice, a cross of black KK females with obese yellow Ay males, which are hyperglycemic, insulin resistant, and obese, was significantly alleviated after 4 weeks of stigmasterol (SMR) treatment, with significantly lower fasting glucose, demonstrating a notable hypoglycemic effect against T2DM. This evidence concerns the gene INS and type 2 diabetes mellitus.