Abstract: AIM To study the effects of ambrisentan on osteopontin in rats with hypoxic pulmonary hypertension. METHODS Forty Sprague Dawley rats were randomly divided into four groups: control group, model group, placebo group and ambrisentan group. Rats in the control group were kept in a normal environment for 4 weeks. Rats in the other groups were kept in a hypobaric chamber for 8 h/day for 4 weeks. For ambrisentan group and placebo group, ambrisentan (5 mg/kg) and normal saline (2 ml) were respectively given at the third week. At the end of 4 weeks, the expression of (osteopontin) OPN in the right ventricle was detected by RT-PCR and Western blot. RESULTS Compared with those in the model group and the placebo group, the expression of OPN in the ambrisentan group was decreased obviously. CONCLUSION Ambrisentan successfully decreases pulmonary artery pressure and restrains the expression of OPN.