Background and Purpose: Drug repositioning is a promising strategy that can be applied to treating pulmonary hypertension, especially in the early stages of the disease. In this study, we aimed to evaluate the synergism between metformin and sildenafil in an experimental model of pulmonary hypertension. Experimental approach: A model of pulmonary hypertension induced by a low dose of monocrotaline (30 mg/kg) was implemented in Wistar rats, and three treatment schemes were compared: metformin (100 mg/kg/day), sildenafil (30 mg/kg/day) and combined therapy of metformin and sildenafil. Right ventricular ejection fraction and pulmonary artery acceleration were estimated by echocardiography, right ventricular hypertrophy was measured with the Fulton index, and hemodynamic changes were obtained by right heart catheterization. Hematoxylin Eosin and Masson’s Trichrome stains evaluated vascular wall thickness and pulmonary fibrosis. With immunohistochemistry were evaluated muscularization (Anti-SMA), adhesion of endothelial cells (CD31) and Proliferation (Ki67). In addition, the toxicity of the model was evaluated with liver and kidney tests. Key Results: The therapeutic regimens reduced cardiac remodeling, the addition of metformin to sildenafil treatment was superior to monotherapy, considerably reducing muscularization and proliferation, reaching normal levels. No differences were found in liver protein and enzyme levels between the groups. Conclusion and Implications: Metformin combined with sildenafil was superior to monotherapy in reducing cell proliferation and muscularization of the pulmonary arterioles. Metformin therapy shows promise as an adjunct to standard sildenafil therapy; This research supports proofs of concept in humans and proposes this drug as a repositioning strategy in pulmonary arterial hypertension.