Hyperglycemia plays crucial roles in vascular disease development, including macrovascular and microvascular diseases from diabetes mellitus (DM). Our previous study demonstrated that Ruellia tuberosa L. (RTL) aqueous and ethanol extracts alleviate hyperglycemia and inhibit insulin resistance in diabetic rats. This study investigated the protective effect of RTL ethanol extract against aorta dysfunction in high‐fat diet (HFD) and streptozotocin (STZ)‐induced type 2 DM (T2DM) rats. Results showed that RTL ethanol extract (100 and 400 mg/kg BW/day) ameliorated serum lipid profiles, including triglyceride, free fatty acid, low‐density lipoprotein cholesterol, very low‐density lipoprotein cholesterol, and high‐density lipoprotein cholesterol levels. It also significantly reduced the level of serum cytokines such as tumor necrosis factor‐α (TNF‐α) and interleukin‐6 in T2DM rats. Additionally, RTL extract decreased endothelin‐1 and endothelial nitric oxide contents, reduced the level of cell adhesion factors, including monocyte chemoattractant protein‐1 and cell adhesion factor vascular cell adhesion molecule‐1, while decreasing content of damage factors, namely tissue factor and von Willebrand factor in aortic tissues of diabetic rats. Equally noteworthy is that RTL extract enhanced the activity of aorta antioxidative enzymes, including superoxidase dismutase and catalase in diabetic rats, suggesting that RTL ethanol extract may ameliorate aorta dysfunction via enhancing aortic antioxidative enzyme activity, which subsequently suppresses aorta endothelial damage‐associated factors in HFD with STZ‐induced T2DM rats.