We previously demonstrated that L-DOPA modulated the vascular α1-adrenergic receptor through GPR143, a G-protein coupled receptor, and sensitized vasomotor tone. In this study, we examined a possible role of GPR143 in the pathogeneisis of pulmonary hypertension (PH). In isolated pulmonary arteries, L-DOPA (1 μM) augmented contractile response to phenylephrine, an α1 adrenergic receptor agonist. We generated GPR143 gene-deficient (Gpr143^-/y) rats and comparatively studied the effect of L-DOPA. L-DOPA did not modify phenylephrine-induced response in the pulmonary arteries of Gpr143^-/y rats, thereby indicating that the action of L-DOPA was mediated by GPR143. We next established monocrotaline (MCT, 60 mg/kg) -induced PH model in wild type (WT) and Gpr143^-/y rats. One month after injection subcutaneously with MCT , the right ventricular systolic pressure (RVSP) was attenuated in Gpr143^-/y rats as compared to the WT rats (49.7 +/- 1.1 mmHg and 41.4 +/- 1.4 mmHg in WT and Gpr143^-/y, p<0.05, N=5). Coordinately, the right ventricle to body weight (RV/BW) (5.4 +/- 0.2 × 10^-4 and 4.7 +/- 0.1 × 10^-4 in WT and Gpr143^-/y, p<0.01, N=12) was also reduced in Gpr143^-/y rats compared to the WT rats. Furthermore, in primary cultures of pulmonary artery smooth muscle cells (PASMCs), the proliferative and migratory capacity of Gpr143^-/y PASMCs after phenylephrine treatment was reduced compared to Gpr143-WT PASMCs. We here provide evidence that GPR143 may be involved in MCT-induced PH in rats by affecting the proliferative and migratory capacity of PASMCs.