Acute pancreatitis is an acute inflammatory response to pancreatic injury. In humans, the magnitude of the response and complications are highly variable and unpredictable. Recent clinical studies demonstrate that all major complications are more common and more severe in patients who are obese. This raises the question of how adipose tissue interacts with the immune response to worsen the severity of acute pancreatitis. Here we review the results of a series of new studies focusing on various fat-associated cytokines (adipokines) that are produced and released in proportion to the amount of visceral adipose tissue in the body. The primary adipokines that have been studied in acute pancreatitis include adiponectin, leptin, visfatin, resistin, and adipose tissue related MCP-1, TNF-a and IL-6. These new data provide strong evidence that susceptibility and severity in acute pancreatitis are associated with a number of these adipokines. Although no specific therapy exists to block the effects of these factors, recognizing the high risk and anticipating inflammation-associated complications of adipokine release is an important part of optimal patient management. For this review, a PubMed search was performed with the terms "acute pancreatitis", "severe acute pancreatitis", and "obesity". Additional searches were conducted to identify recent reviews on adipokines, Finally, PubMed searches on specific adipokines, including adiponectin, leptin, visfatin and resistin were conducted focusing on acute pancreatitis and systemic inflammation.