This study provided evidence for the role of tropisetron on type 2 diabetes mellitus via modulating the insulin signaling cascade (insulin, phosphorylated insulin receptor substrate 1, phosphorylated protein kinase B, and glucose transporter 4), improving lipid/glucose profile, decreasing inflammatory markers (receptor for advanced glycation end products, and phosphorylated nuclear factor kappa B p65), as well as increasing 5-HT and reducing β-catenin. Here, IRS1 is linked to diabetes mellitus.