Chronic exposure to hypoxia (CH), a common adverse consequence of most pulmonary disorders, can lead to a sustained increase in pulmonary arterial pressure (PAP), right ventricular hypertrophy and is, therefore, closely associated with heart failure and increased mortality. Ghrelin, originally identified as an endogenous growth hormone secretagogue, has recently been shown to possess potent vasodilator properties – likely involving modulation of the vascular endothelium and its associated vasoactive peptides. In this study we hypothesized that ghrelin would impede the pathogenesis of pulmonary arterial hypertension (PAH) during CH. PAP was continuously measured using radio-telemetry, in conscious male Sprague Dawley rats, in normoxia and during two weeks of CH (10% O₂). During this hypoxic period, rats received a daily subcutaneous injection of either saline or ghrelin (150 µg/kg). Subsequently, heart and lung samples were collected for morphological, histological and molecular analyses. CH significantly elevated PAP in saline-treated rats, increased wall thickness of peripheral pulmonary arteries and, consequently, induced right ventricular hypertrophy. In these rats, CH also lead to the over-expression of endothelial nitric oxide synthase (eNOS) mRNA and protein as well as endothelin-1 (ET-1) mRNA within the lung. Exogenous ghrelin administration attenuated the CH-induced over-expression of eNOS mRNA and protein as well as ET-1 mRNA. Consequently, ghrelin significantly attenuated the development of PAH, pulmonary vascular remodeling, and right ventricular hypertrophy. These results demonstrate the therapeutic benefits of ghrelin for impeding the pathogenesis of pulmonary hypertension and right ventricular hypertrophy, particularly in subjects prone to CH (e.g. pulmonary disorders).