Acute pancreatitis is a serious inflammatory condition. Research has shown an increase in the number of pancreatitis-associated hospitalizations, with a marked decline in the mortality rates down to 0.79% in patients with acute pancreatitis and 0.26% in patients with exacerbation of chronic pancreatitis. Up to one-third of patients develop pancreatic tissue necrosis, with a mortality rate of 30%. One of the mechanisms is the disturbances in pancreatic microcirculation due to the release of endothelin, a long-acting vasoconstrictor. The development of pancreatitis causes the release of other inflammatory mediators, which reduce blood flow in the microcirculation. The activation of intracellular trypsinogen initiates a cascade of mechanisms in pancreatitis. There is no specific treatment for acute pancreatitis. Protease inhibitors are not effective in treating severe acute pancreatitis. There is an important role of low-molecular-weight heparin in attenuating necrosis and restoring perfusion of the pancreas. Other drugs used are endothelin receptor antagonists, antagonist of interleukin-1 and interleukin-6 receptors, α-tocopherol, tumor necrosis factor-α and platelet-activating factor inhibitors, acetylsalicylic acid, and local intra-arterial injection of lidocaine. The prophylactic use of antibiotics is not recommended. The treatment outcome of acute pancreatitis is still unsatisfactory.