Background A number of reports based on both animal experiments and clinical investigations have pointed out that total parenteral nutrition (TPN) suppresses the function of the exocrine pancreas. Even though pancreatic hypotrophy and dysfunction resulting from TPN may be explained by several mechanisms, the clinically most important cause is that nutrients in circulation affect pancreatic secretion. The effect of nutrients on the exocrine pancreas is still controversial. The aim of the present study was, therefore, to clarify the influence of intravenous amino acids and hypertonic glucose in TPN solution on the exocrine pancreas. Methods Three mixed TPN solutions, consisting of 30% or 50% glucose or of 14% amino acids, were employed. Twenty-four male Sprague-Dawley rats were randomly divided into four groups, six rats in each group, including a control group and one group receiving each of the three TPN solutions. All animals were killed after 10 days of TPN. Body weight, pancreatic content, and enzyme levels in the pancreas were measured. Results Compared with the control group, pancreatic wet weight was lower in all TPN groups. Glucose significantly decreased the content and concentration of pancreatic protein, but amino acids did not alter the concentration of protein. The level of amylase was lower in all parenterally fed groups, with a greater decrease in the groups treated with amino acids and 30% glucose than with 50% glucose. Trypsin levels in all groups receiving TPN were markedly higher than in the control group. Conclusion TPN results in atrophy of the pancreas, but trypsin levels increase with TPN treatment. Glucose elevates the amylase level in the pancreas, while amino acids suppress pancreatic amylase. Amino acids used as a source of protein maintain normal pancreatic protein levels.