Acute pancreatitis (AP) is a common disease in which the underlying mechanisms of the local initiating events in the pancreas, the systemic dissemination of the inflammatory response and the development of remote organ dysfunction have not been fully clarified. AP is still associated with substantial morbidity and mortality. Clinical therapeutic strategies for AP have so far been mainly directed at supportive critical care. After the initial injury to the pancreatic acinar cells, the inflammatory mediators released from the inflamed acini trigger activating cascades through immunocompetent cells, leading to the development of systemic inflammatory response syndrome and multiple organ dysfunction syndrome. These damaged, inflamed acinar cells interact with activated, immigrated immune cells and inflammatory mediators and therefore amplify the inflammatory response in AP. Of these immune cells, neutrophils, monocytes/macrophages and T lymphocytes play critical roles in the pathogenesis of AP. Substantial evidence exists demonstrating the importance of inflammatory mediators such as cytokines, chemokines and adhesion molecules in the initiation of the progression of AP. Inflammatory mediators in damaged, inflamed acinar cells and activated immunocompetent cells are closely regulated through cellular signalling pathways, e.g. those involving nuclear factor-κB, mitogen-activated protein kinase, reactive oxygen species and protein kinase C. Therefore, cellular and molecular events are crucial to the pathophysiological mechanisms underlying AP. Single- or multi-modal treatment regimens directed at regulating different steps in the signalling pathways could represent future modes of management.