Background Pulmonary hypertension is a risk factor for morbidity and mortality in septic shock. Pulmonary hypertension increases the right ventricular afterload, which tends to reduce the right ventricular output, leading to right ventricular dysfunction. Sildenafil has been largely used in the treatment of pulmonary arterial hypertension, but its effects in sepsis are unknown. The aim of this study was to investigate the hypothesis that sildenafil is able to attenuate endotoxin-induced pulmonary hypertension in a porcine model. Further, we investigated the effects on hemodynamic and oxygenation functions. We also evaluated lung morphology and the effect on plasma cytokine and troponin response. Methods Twenty pigs in which endotoxeamia was induced through intravenous bacterial lipopolysaccharide endotoxin (LPS) infusion (4µg/kg/h) were randomly assigned to Control group (n=10) – which received saline solution; or to Sildenafil group (n=10) – which received sildenafil orally (100 mg) previous the endotoxeamia. Results LPS induced a significant pulmonary hypertension with an increase in pulmonary arterial pressure, pulmonary vascular resistance index, end-diastolic volume of the right ventricle and also a decrease in PaO2/FiO2. Pulmonary and systemic arterial pressures were significantly lower in the Sildenafil group and sildenafil prevented the LPS effect on the end-diastolic volume of the right ventricle. Sildenafil maintained oxygenation with superior PaO2/FiO2 and lower oxygen extraction rate, but had no effect on intrapulmonary shunt. All cytokines and troponin increased after LPS infusion in both groups similarly. The LPS induced lung lesions, but there were no intergroup differences in the histological scoring system. Conclusion Sildenafil attenuated endotoxin-induced pulmonary hypertension preserving right heart function and maintained oxygenation without effecting shunt fractioning. However, caution should be taken due to the potential systemic vasodilatory effect. Sildenafil did not attenuate lung lesions and did not presented an anti-inflammatory effect in a porcine model of endotoxaemia.