Early events critical for the development acute pancreatitis are considered. The possible initiating mechanisms of intracellular trypsinogen activation are discussed. Essential attention is paid to the role of cathepsin B, intraacinar [Ca2+] increase and free radicals generation in the premature zimogen activation. It is demonstrated, that the trypsinogen activation alone may not be sufficient to cause acinar cell injury. Some factors, other than active trypsin, play a main role in the pancreatic damage and in the development of systemic complications of acute pancreatitis.