OBJECTIVE: Inflammation and over-proliferation of pulmonary artery smooth muscle cells (PASMCs) have been considered as the major pathological features of pulmonary hypertension (PH). Here we aimed to determine that mesenchymal stem cells (MSCs) suppress the expressions of calcineurin (CaN) and nuclear factor of activated T-cells (NFAT) in pulmonary artery of rat, and accomplish the therapeutic effect on PH. METHODS: By transplantation of Human umbilical cord derived MSCs cultured in serum free medium into monocrotaline (MCT) induced PH rats, we assessed the therapeutic effects of MSCs on PH. Meanwhile, the levels of TNF-a in lung tissue and plasm, the expressions of CaN and NFATc2 in pulmonary arteries were assessed. RESULTS: In the rat model of MCT induced PH, the expression of TNF-a could observed in lung tissue, and the plsma TNF-a level also increased evidently. Meanwhile, accompany with the evident medial hypertrophy of pulmonary muscular arterioles and hemodynamic changes, the expressions of CaN and NFATc2 in pulmonary arteries were significantly up-regulated. Transplantation of MSCs cultured in serum free medium decreased the TNF-a level not only in the lung tissue but also in plsma. Meanwhile, the expressions of CaN and NFATc2 in pulmonary arteries were down-regulated. Under the background of above effects of MSCs, medial hypertrophy of pulmonary muscular arterioles and hemodynamic abnormality were improved evidently. CONCLUSIONS: Administration of MSCs in PH could suppress the production of TNF-a, and then down-regulate the expression of CaN and NFATc2 in pulmonary arteries, which finally lead to the suppressive effect to proliferation of PASMCs and achieve the treatment to PH.