Background：Pulmonary hypertension (PH) is characterized by a progressive increase in pulmonary vascular resistance, structural remodeling of the pulmonary vasculature, finally, right ventricular failure and death. One trigger of PH is hypoxia which chronically leads to vascular proliferation and remodeling. The proliferation of smooth muscle cells is now recognized to play a significant role in the remodelling of small pulmonary arteries. The mammalian target of rapamycin (mTOR) also known as mechanistic target of rapamycin has been reported to be an important signal pathway which involevd in cell proliferation. However, whether rapamycin could attenuate hypoxia-induced pulmonary hypertension by inhibiting cell proliferation and the possible signal pathways are still unknown.Objective：To investigate the effect of rapamycin on hypoxia-induced pulmonary hypertension andits possible mechanism.Methods：8-week male C57BL/6 mice were exposed to either normobaric hypoxia(10% oxygen) ornormoxic condition (21% oxygen), with or without rapamycin (3mglkg*d, i.p.) orcarboxymethylcellulose as vehicle from the first day. At 0, 1，2, 3 and 4 weeks(6 mice in eachgroup for each time point), The right ventricular pressure(RVSP) of mice was measured by usingclosed-chest cardiac puncture technique, and then, the mice were sacrificed, heart and lung werecollected. The index of right ventricular hypertrophy(RVHI), that is the ratio of the right ventricularweight to left ventricular weight plus the interventricular septum was calculated. Histological andimmunohistochemical measurement were used to assess the distal vascular remodeling.Results：The RVSP and RVHI of control mice were 16.94 1 0.30 mmHg and 0.21810.0047respectively. After 1, 2, 3 and 4 weeks housed in hypoxia, the RVSP gradually increased to19.03士0.69 mmHg (12.64%±5%, p<0.01), 21.22±0.71 mmHg (25.71%±6%, p<0.01), 21.64±0.49 mmHg (28.04%t4%, p<0.01) and 22.27士0.19 mmHg (31.69%±3%, p<0.01) compared with 0 week. TheRVHI gradually raised to 0.2324±0.0034 (6.8%±2.5%, p>0.05), 0.2527±0.0081 (16.49%士6%,p