Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear receptor that functions as a transcription factor to regulate adipogenesis and metabolism by binding to PPAR response elements (PPAREs) in the promoter region of various target genes. Activation of PPARgamma suppresses smooth muscle cell proliferation and migration. This chapter discusses the potential protective role of PPARgamma and its downstream signaling cascades in the development of pulmonary arterial hypertension. Furthermore, the chapter also provides an overview on the cellular and molecular mechanisms involved in PPARgamma-mediated inhibitory effect on pulmonary vascular remodeling, a major contributor to the elevated pulmonary vascular resistance in patients with pulmonary arterial hypertension.