The pathogenesis of chronic pancreatitis and pain syndrome had not been fully studied. The aim of the study was to evaluate the interrelation of fibrotic and ischemic changes in the parenchyma of pancreas, and pancreatic duct pressure in the pathogenesis of chronic pancreatitis. In a prospective study, a morphological, the immunohistochemical study of pancreatic preparations was performed, and the indicators of tissue oximetry and pancreatic duct pressure were studied intraoperatively in 40 patients operated for chronic pancreatitis. It was found that with the progression of fibrotic changes in the pancreatic tissue of patients with chronic pancreatitis, there was an increase in TGF-β1 expression (р < 0.001), an increase in the number of pancreatic stellate cells (r = 0.32, р < 0.05), a decrease in glycogen (ischemia marker). The intraoperative direct measurement revealed a high pancreatic duct pressure: 34.2 (26.6; 45.3) mm Hg, a decrease in oxygenation of the pancreatic tissue that correlate with a degree of fibrosis. The pancreatic tissue in chronic pancreatitis has chronic hypoxia associated with fibrosis and increased pancreatic ductal hypertension. So, secondary pancreatic ischemia can be a significant factor in the progression of fibrosis and chronic pain syndrome in chronic pancreatitis.