Abstract. Diabetes is associated with a higher prevalence of cardiovascular disease, and recently it was shown as a risk factor in the development of pulmonary arterial hypertension (PAH). Regarding the systemic circulation, it is well known that diabetes is associated with vascular dysfunction and an elevation in the systemic pressure, being the endothelial function in aorta compromised in diabetic rats (1, 2). However, it is not consensual that PAH is caused by endothelial dysfunction (3, 4, 5). Aim. Herein we have investigated the effect of different stages of diabetes on the contractility machinery and endothelial function in the pulmonary and systemic circulation. Methods. We used 2 pathological animal models: the high-fat (HF) animal, which is submitted to 3 weeks of 60% lipid-rich diet and that represents a prediabetic stage, and the high-fat/high-sucrose (HFHSu) animal, which is submitted to a combined diet of 60% lipid-rich diet and 35% sucrose in drinking water for 14 weeks and that represents an early type 2 diabetes stage. Pathological animal models were compared with age-matched controls. Rats were anesthetized with pentobarbitone (60 mg/kg. ip.) and the pulmonary and aortic arteries were removed and dissected. Contractility was evaluated by small vessels myography in the rings of pulmonary and aortic arteries in response to increasing doses of prostaglandin F2α (PGF2α) and expressed as % of the contractile response against 80mM of external K+ (KPSS). Endothelial function was evaluated by monitoring the relaxation effect of acetylcholine over the contraction induced by PGF2α. NO levels in aortic and pulmonary arterial trees were measured. Results. PGF2α produced a dose-dependent increase in arterial contractility in pulmonary and aortic arteries in control, HF and HFHSu animals. Pulmonary artery contractility to PGF2α was significantly enhanced in HF animals, while it was diminished in the HFHSu animals (PGF 30µM, expressed as % of KPSS 80mM: control=21.8±2.8, n=20; HF=32.2±4.4 (p<0.001), n=12; HFHSu=10.6±1.8 (p<0.001), n=7. In the aorta we found that the contractile response to PGF2α increased in both diabetic models (PGF 10µM: control=75.3±10.8, n=10; HF=104.8±19.3, n=6; HFHSu=129.4±13.9, n=9). Endothelial function was unaffected in pulmonary artery in prediabetes and early type 2 diabetes animal models, while it was compromised in the aorta in the HFHSu animals, as the dose-response relaxation curve to ACh was significantly decreased in relation to control animals (p<0.001; control n= 10; HFHSu n=8). Conclusions. In diabetes contractility to PGF2α is altered in both the pulmonary artery and aorta. Diabetes affects endothelial function in the aorta but not in the pulmonary artery. This suggests that the pulmonary artery is more resistant to diabetes-induced endothelial dysfunction.