Nitric oxide (NO) is a major endothelium dependent vasomediator and growth inhibitor. NO is catalysed by NO synthase (NOS), and whether the expression of NOS is altered in association with the ventricular hypertrophy is not known. NO can also produce peroxynitrite, which activates matrix metalloproteinases (MMPs). The purposes of this study were to determine the gene expression of endothelial NOS and MMP-2 in the lung in a rat model of pulmonary hypertension. Sprague-Dawley rats were treated with monocrotaline (MCT) (60 mg/kg) to produce pulmonary hypertension. The mean body weight significantly decreased in the MCT group compared with the control group. The RV/(LV+septum) ratio significantly increased in the MCT group compared with the control group on days 14 & 28. The expression of eNOS mRNA significantly increased in the MCT group compared with the control group (3.51±1.18 vs 1±0.37) on day 28. Serum NO level did not show significant change in either group. Serum MMP-2 level (254.21±36.27 ng/mL vs 198.37±10.57 ng/mL) and MMP-2 gene expression (4.55±1.98 vs 1±0.34) significantly increased in the MCT-treated rats compared with the control group on 28 day. These data suggest that elevated eNOS expression may be responsible for the activation of MMP-2. The causal relationship between eNOS and MMP-2 and their role in pulmonary hypertension require further investigations.