Background and objectives. Kallistatin, a serine proteinase inhibitor, exerts its effect by vascular repair, angiogenesis inhibition, strong vasodilation, inhibition of vascular endothelial growth factor (VEGF), anti-inflammation, and anti-apoptosis. We hypothesized as to whether it has a protective role in pulmonary arterial hypertension (PAH). Methods. The study included 5 subgroups (78 patients; 44 male): Eisenmenger syndrome (n=16), PAH with left to right shunt (n=20), idiopathic PAH (n=7), patients with left to right shunt without PAH (n=19), and patients with innocent heart murmur (n=16). Physical examination, chest radiography, electrocardiography, and transthoracic echocardiography (TTE) were performed for each patient. PAH diagnosis was confirmed by catheterization. Serum kallistatin, tumor necrosis factor alpha (TNF-α), Interleukin-10 (IL-10) and N-terminal pro b-type natriuretic peptide (NT-proBNP) levels were studied for each patient.Results. The lowest median kallistatin value was found in Eisenmenger syndrome: 1.19 (0.87-3.30) μg/ml. The highest value belonged to control group with innocent murmur: 2.89 (1.19-5.66) μg/ml. Serum levels of kallistatin were significantly lower in patients with PAH (p<0.05). TNF-α values were increased and IL-10 values were decreased in pulmonary hypertension. However; no correlation was found between kallistatin levels and cytokines.Conclusions. Kallistatin may have a protective effect in pulmonary arterial hypertension by repairing vascular damage, inhibition of angiogenesis, strong vasodilator effect, inhibiting VEGF, and anti-inflammatory mechanism of action. To our knowledge, our study is the first one that shows the role of kallistatin in pulmonary hypertension. Kallistatin may represent a promising novel therapeutic approach for pulmonary hypertension in the near future.