Peroxisome proliferator-activated receptor (PPAR)-γ is reduced in pulmonary arteries (PAs) of patients with PA hypertension (PAH), and we reported that deletion of PPARγ in smooth muscle cells (SMCs) of transgenic mice results in PAH. However, the sequelae of loss of PPARγ in PA endothelial cells (ECs) are unknown. Therefore, we bred Tie2-Cre mice with PPARγ^flox/flox mice to induce EC loss of PPARγ (Tie2 PPARγ^−/−), and we assessed PAH by right ventricular systolic pressure (RVSP), RV hypertrophy (RVH), and muscularized distal PAs in room air (RA), after chronic hypoxia (CH), and after 4 wk of recovery in RA (Rec-RA). The Tie2 PPARγ^−/− mice developed spontaneous PAH in RA with increased RVSP, RVH, and muscularized PAs vs. wild type (WT); both genotypes exhibited a similar degree of PAH following chronic hypoxia, but Tie2 PPARγ^−/− mice had more residual PAH compared with WT mice after Rec-RA. The Tie2 PPARγ^−/− vs. WT mice in RA had increased platelet-derived growth factor receptor-β (PDGF-Rβ) expression and signaling, despite an elevation in the PPARγ target apolipoprotein E, an inhibitor of PDGF signaling. Inhibition of PDGF-Rβ signaling with imatinib, however, was sufficient to reverse the PAH observed in the Tie2 PPARγ^−/− mice. Thus the disruption of PPARγ signaling in EC is sufficient to cause mild PAH and to impair recovery from CH-induced PAH. Inhibition of heightened PDGF-Rβ signaling is sufficient to reverse PAH in this genetic model.