Environmental conditions such as extreme ambient temperatures and high altitudes can trigger the development of ascites syndrome that results in significant economic loss estimated at $1 billion annually. Pulmonary hypertension (PH) in poultry has been recognized for many years at high altitude. Low oxygen partial pressure at high altitudes stimulates cardiac output which results in higher blood pressure and increased blood volume in the lung that lead to PH. PH causes right ventricular hypertrophy and dilation, valvular insufficiency and right ventricle failure followed by ascites syndrome. Collagen is the most abundant protein in vertebrates. It is the major component of extracellular matrix (ECM) and plays a dominant role in maintaining the structure of tissues. In normal tissue, there is a balance between ECM collagen synthesis and degradation. The only enzymes capable of breakdown of collagen are matrix metalloproteinases (MMPs). Degradation of collagen by MMPs, are suggested to contribute to tissue remodeling. In this study it was hypothesized that hypoxic-induced PH at high altitude causes adverse changes in ECM of broiler’s lung and liver that can lead to ascites syndrome. To investigate this hypothesis male broilers (Ross 308) were raised at two regions of high altitude (Shahrekord; 2061 meters above sea) and sea level ( Rasht ). Similar nutritional conditions were employed in both regions, except that feed restriction was applied in Shahrekord at week 4. Lung and liver samples were taken at weeks 2,3,4,5 and 6 from 20 broilers. Histopathological (H E staining) and morphological analysis, collagen content measurement (OH-Proline Measurement) and MMPs levels evaluation (gelatin zymography) were performed. Statistical analysis was carried out by tTest procedure of SAS. Lungs of broilers from Rasht had normal appearance whereas those of Shahrekord were congested and in some cases covered with a sticky yellowish film. Presence of large amounts of blood clots and lung congestion can be indication of PH in Sharekord broilers. In addition, histological analysis showed hemorrhagic and constricted parabronchi. Liver in both Rasht and Shahrekord broilers had normal appearance but histological analysis showed dilation of liver sinusoids in Sharekord broilers. For the first time we have evaluated MMPs levels in lung and liver of broilers at high altitude and demonstrate that MMP-2 level increases in lung and liver at low oxygen pressure. Also, for the first time we have measured collagen content of broilers’ lung and liver and report that increased MMP-2 level caused collagen degradation and tissue remodeling in sharekord broilers. This was evident in histolog