Objective: The main cause of increased morbidity - mortality and reduced quality of life in diabetic patients is the diabetic vascular disease. In diabetic vascular disease, there is an increase in insulin-resistant, pro-inflammatory mediator, and reactive oxygen species (ROS); and impairment in beta-pancreatic cells function. On the other hand, nicotine can inhibit pro-inflammatory mediators; and increase insulin sensitivity, pancreatic beta-cell function, and antioxidants level. As nicotine contained in tobacco leaf, this research was aimed to explore the effect of Nicotiana tabacum leaves extract toward fasting blood glucose levels and tail arterial wall changes of Type 2 Diabetes Mellitus (T2DM) rat. Methods: In this study we use twenty five 8-10 weeks old male diabetic Wistar rats. T2DM was modelled through high fat diet for 16 days followed by 22.5 mg/kg of body weight Streptozotocin intraperitoneal administration. Fasting Blood Glucose (FBG) level beyond 180 mg/dL was considered as T2DM. Total of 25 rats were assigned into 5 groups. Sham and STZ-HFD groups assigned as non-diabetic and diabetic controls respectively. Groups P1, P2, and P3 received tobacco leaf extract with dose of 90, 180, 270 mg/kg body weight respectively for 27 days. Weekly FBG level, Tail Arterial Wall Thickness, Lumen Radius, and Wall to Lumen Ratio was measured. Results: Tobacco leaf extract at all doses showed significant reduction in fasting blood glucose level compared to STZ-HFD Group during day 27 (Mann-Whitney, p < 0.05). STZ-HFD has 16% thicker Wall Artery than Sham. P1, P2, and P3 has 2%, 13%, and 23% thinner Wall Artery compared to STZ-HFD. STZ-HFD has 11% higher Wall to Lumen Ratio compared to Sham Group. Group P1, P2 and P3 showed 26%, 24%, and 23% lower Wall to Lumen Ratio compared to STZ-HFD Group. Conclusion: Administration of nicotiana tabacum leaf extract can prevent arterial wall thickness and reduce FBG level in T2DM