Ghrelin and melatonin are produced in the central nervous system and in the gastrointestinal tissues; ghrelin in the stomach, and melatonin - in the liver and in the intestine. Both ghrelin and melatonin have been reported to protect the gastric mucosa against acute lesions and to influence gastrointestinal motility and secretions, however the physiological significance of these peptides in the gastrointestinal tissues remains unknown. In spite of the presence of ghrelin and melatonin receptors in the pancreatic tissue little is known about the role of these peptides in the pancreas. It is very likely that both ghrelin and melatonin, which are released from the gastrointestinal tract in relation to food ingestion, could be implicated in the postprandial stimulation of pancreatic enzyme secretion though the activation of cholinergic entero-pancreatic reflex and CCK release. Our experimental studies have shown that exogenous melatonin, as well as this produced endogenously from its precursor; L-tryptophan, strongly stimulates pancreatic amylase secretion when given intraperitoneally, or into the gut lumen. Intraduodenal administration of ghrelin also increases pancreatic enzyme secretion. This was accompanied by significant increases of CCK plasma levels. Above pancreatostimulatory effects of luminal administration of melatonin or ghrelin were completely reversed by bilateral vagotomy, capsaicin deactivation of sensory nerves or pretreatment of the rats with CCK1 receptor antagonist; tarazepide. Our previous findings have revealed that melatonin, as well as its precursor; L-tryptophan, effectively protects the pancreas against the damage induced by caerulein overstimulation. The beneficial effects of melatonin and L-tryptophan on the pancreas have been related to the ability of melatonin to scavenge the radical oxygen species (ROS), to activate antioxidative enzymes and to modulate the cytokine production. It has been previously shown that systemic application of ghrelin attenuated acute pancreatitis activating the immune defense mechanisms. Our recent data demonstrate that ghrelin is able to prevent pancreatic inflammatory damage though the activation of central nervous mechanisms leading to the improvement of antioxidative properties of pancreatic tissue. The results of experimental studies indicated that melatonin and ghrelin could take a part in the protection of pancreatic tissue against the damage under physiological conditions.