Pulmonary hypertension syndrome also known as ascites syndrome is one of the major causes of mortality and economic loss in broiler industry. However, the pathogenesis of this syndrome is not fully elucidated yet, specifically at a cellular-molecular level. Accordingly, aim of the first experiment of our study was to investigate extracellular matrix (ECM) remodeling of four important tissues involved in pathogenesis of ascites syndrome including: right ventricle (RV), left ventricle (LV), lung and liver. Cold temperature is one of the primary triggers for ascites syndrome which was used in this research as the induction factor. 160 one-day-old chicks (Ross 308) were divided into two groups (four pen replicates each, 20 chicks/pen) of NT (normal temperature) and CT (cold temperature). On day 21, chickens in CT group were exposed to the cold temperature whereas NT chicks continued at normal temperature. At 39 and 46 days of age two chickens with a body weight around the pen average were selected from each pen and sacrificed after collecting blood samples. Then, tissue samples from RV, LV, lung and liver were obtained for ECM investigations. Histopathological studies were done by H E staining of tissue samples. Collagen and elastin content of tissue were measured by tissue digestion in CNBr in 70% formic acid and then measuring amount of hydroxyproline via a spectrophotometry method using Chloramine-T and Ehrlich's reagents. Matrix metalloproteinases (MMPs) assessments were carried out by gelatin zymography. Data were analyzed in a completely randomized design using the GLM procedures of SAS software. Compared with NT chickens, CT ones were pulmonary hypertensive and had greater ascites mortality. Furthermore, CT birds showed considerable histopathological changes in their RV, LV, lung and liver, leading to loss of normal tissue structure. They also had higher Pro and Active MMP-2 levels, indicating increased production and activity of this enzyme in cold-exposed chickens. In CT birds, amounts of total and soluble collagen decreased in RV, LV and liver and increased in lung, insoluble collagen increased in lung and liver and elastin increased in lung tissue. These findings are indicative of ECM remodeling in cold-exposed birds. The main objective of the second experiment was to evaluate effects of doxycycline (DOX), as a MMP inhibitor, on ECM remodeling of RV, LV, lung and liver in cold-exposed broilers. 240 one-day-old chicks (Ross 308) were divided into three groups (four pen replicates each, 20 chicks/pen) of DX0, DX40 and DX80 which consumed 0, 40 and 80 mg/kg BW/d of DOX from day 19 onward, respectively. All groups exposed to the cold temperature from day 21 onward. Compared with DX0, DX40 and DX80 chickens had decreased ascites mortality. Also, they showed alleviated histopathological changes, reduced levels of Pro and Active MMP-2 and higher total and soluble collagen in RV, LV, lung and liver. They had higher contents of insoluble collagen in RV and LV and lower contents of this protein in lung and liver. These data can be indicative of alleviative effect of DOX on ECM remodeling and ascites incidence in cold-exposed chickens. Main purpose of the third experiment was to investigate effects of feed restriction on ECM remodeling in cold-exposed broilers. 160 one-day-old chicks (Ross 308) were divided into two groups (four pen replicates each, 20 chicks/pen) of Ad (free access to feed throughout the experiment) and FR (restricted access to the feed from day 7 to 14). All groups exposed to the cold temperature from day 21 onward. In comparison with Ad chickens, FR birds had decreased ascites mortality. They also showed decreased histopathological alterations and lower levels of Pro and Active MMP-2 in RV, LV, lung and liver tissues. Furthermore, they had greater amounts of total (RV, LV) and soluble (RV, LV and liver) collagen and lower contents of insoluble collagen (LV, lung and liver). These results can suggest that feed restriction has an inhibitory effect on ECM remodeling in cold-exposed broilers. In conclusion, results of these three studies may suggest that pulmonary hypertension induces ECM remodeling and triggers series of events which can lead to ascites syndrome, whereas, MMP inhibitors (doxycycline in this study) as well as feed restriction can stop this procedure via inhibiting MMP-2 production and activation leading to alleviated ascites incidence. Keywords: Broilers, Ascites syndrome, Doxycycline, Feed restriction, Extracellular matrix remodeling, Matrix metalloproteinase, Collagen, Elastin