Pulmonary arterial hypertension (PAH) is a progressive disorder characterised by pulmonary vascular constriction and remodelling which ultimately leads to right heart failure. Recent evidence suggests an association between type II diabetes (T2D) and PAH. Epidemiological data show that patients with T2D are at increased risk of developing PAH (1). Clinically, PAH patients have increased insulin resistance (2), while experimentally, rodent models of insulin resistance develop PAH (3,4). However, the mechanisms associating T2D with the development of PAH are poorly understood. The aim of the current study was to investigate changes in expression of key genes related to the development of PAH in lung tissue derived from a rat model of T2D. Right ventricular hypertrophy (RVH), an indicator of PAH phenotype, was also assessed in T2D rats. Methods: T2D was induced in 12 week old male Wistar rats (n=6) by feeding a high fat diet (22%) for 12 weeks, with a single dose of streptozotocin (30mg/kg, i.p.) given on week 4. Control rats (n=5) were fed standard diet and injected with vehicle. T2D was verified by hyperglycaemia and hyperinsulinaemia. Rats were sacrificed at 24 weeks old via sodium pentobarbitone (5mg/100g, i.p.). Whole lung gene expression of bone morphogenetic protein receptor type 2 (BMPR2), tryptophan hydroxylase 1 (Tph1; the rate-limiting enzyme in the synthesis of serotonin), the receptor for advanced glycation end products (RAGE), endothelial nitric oxide synthase (NOS-3) and NADPH oxidase 4 (NOX-4) was analysed by real time PCR and expressed as relative quantity. RVH was expressed as the ratio of the weight of the right ventricle to the weight of the left ventricle plus septum. Data were analysed by unpaired Students t-test and expressed as mean ± SEM. Results: BMPR2 gene expression was downregulated in lungs of T2D rats (control: 1.0 ±0.31 vs T2D: 0.02 ± 0.09, p≤0.001). Additionally a reduced expression of RAGE (control: 1.0 ± 0.21 vs T2D: 0.48 ± 0.20, p≤0.05) and NOX-4 (control: 1.0 ± 0.21 vs T2D: 0.14 ± 0.16,p≤0.05) was observed in the lungs of T2D rats. No significant alteration in Tph1 (control: 1.0 ± 0.36 vs T2D: 0.43 ± 0.48) or eNOS (control: 1.0 ± 0.38 vs T2D: 1.41 ± 0.64) expression was found. No significant alteration in RVH was observed between control rats (0.232 ± 0.024) and T2D rats (0.246 ± 0.010). Conclusions: This study has shown reduced gene expression of BMPR2, RAGE and NOX-4 in the lungs of T2D rats. A reduction in BMPR2 gene and protein expression has been shown in PAH patients and in animal models of disease (5), therefore this may pre-dispose T2D rats to development of PAH. Despite these changes in gene expression, T2D rats did not show RVH. Ascertaining whether pulmonary vascular remodelling occurred in T2D rats is important and currently ongoing.