Background: Acute pancreatitis is a dangerous disease that may be complicated by multi-organ failure. Adropin is a metabolic hormone expressed in many tissues including endothelium and pancreas. Dexamethasone has protective effects against acute pancreatitis. Aim: To assess the potential protective effect of adropin on pancreatic and pulmonary changes in L-arginine induced acute pancreatitis in rats, in comparison to that of dexamethasone. Materials and Methods: Rats were randomly separated into equal groups including control, acute pancreatitis (AP), acute pancreatitis pretreated with adropin (AP+Adro), and acute pancreatitis pretreated with dexamethasone (AP+Dexa) groups. In AP group, acute pancreatitis was induced on the 5th day of the start of study by two intraperitoneal (i.p.) injections of L-arginine. In AP+Adro and AP+Dexa groups, rats received a single daily i.p. dose of adropin (34-76) (2.1 μ g/kg) and of dexamethasone (2 mg/kg), respectively for the first 5 days. In the 5th day, acute pancreatitis was induced as in AP group, then the rats were left for 24 hours then sacrificed and blood, lungs, and pancreas were collected. Results: In AP group, there was a significant increase in; serum (amylase, lipase, interleuken-1 beta & tumor necrosis factor alpha), pancreatic (MDA, NO & Bcl-2) and pulmonary (MDA, NO & Bcl-2), with a significant decrease in; serum adropin, pancreatic TAC and pulmonary TAC. Additionally, there were strong positive immunoreactions for; NF-κB (in pancreas and lung), and TNFα (in lung). Marked histological alterations were observed in both pancreatic and lung tissues. On pretreatment by either adropin or dexamethasone, the changes were ameliorated as compared to the AP group. Conclusion: Acute pancreatitis had a detrimental influence on exocrine pancreatic function and lung structure, which may be preserved by adropin as well as dexamethasone therapy through their anti-inflammatory, antioxidant, and pro-apoptotic activities. Thus, adropin and dexamethasone may be used to prevent acute pancreatitis and the associated lung injury.