Increased serotonin serum levels have been proposed to play a key role in Pulmonary Arterial Hypertension (PAH) by regulating vessel tone and vascular smooth muscle cell proliferation. An intact serotonin system, which critically depends on a normal function of the serotonin transporter (SERT), is required for the development of experimental pulmonary hypertension in rodents exposed to hypoxia or monocrotaline. While these animal models resemble human PAH only with respect to vascular media remodeling, we hypothesized that SERT is likewise required for the presence of lumen-obliterating intima remodeling, a hallmark of human PAH reproduced in the Sugen/hypoxia (SuHx) rat model of severe angioproliferative pulmonary hypertension. Therefore, SERT wild type (WT) and knock-out (KO) rats were exposed to the SuHx-protocol. SERT-KO rats, while completely lacking SERT, were hemodynamically indistinguishable from WT rats. After exposure to SuHx, similar degrees of severe angioproliferative pulmonary hypertension and right ventricular hypertrophy developed in WT and KO rats (right ventricular systolic pressure 60 vs 55 mmHg, intima thickness 38 vs 30%, respectively). In conclusion, despite its implicated importance in PAH, SERT does not play an essential role in the pathogenesis of severe angio-obliterative pulmonary hypertension in rats exposed to SuHx.