Amino acids derived from ingested protein are potential substrates for gluconeogenesis. However, several laboratories have reported that protein ingestion does not result in an increase in the circulating glucose concentration in people with or without type 2 diabetes. The reason for this has remained unclear. In people without diabetes it seems to be due to less glucose being produced and entering the circulation than the calculated theoretical amount. Therefore, we were interested in determining whether this also was the case in people with type 2 diabetes. Ten male subjects with untreated type 2 diabetes were given, in random sequence, 50 g protein in the form of very lean beef or only water at 0800 h and studied over the subsequent 8 h. Protein ingestion resulted in an increase in circulating insulin, C-peptide, glucagon, alpha amino and urea nitrogen, and triglycerides; a decrease in nonesterified fatty acids; and a modest increase in respiratory quotient. The total amount of protein deaminated and the amino groups incorporated into urea was calculated to be approximately 20-23 g. The net amount of glucose estimated to be produced, based on the quantity of amino acids deaminated, was approximately 11-13 g. However, the amount of glucose appearing in the circulation was only approximately 2 g. The peripheral plasma glucose concentration decreased by approximately 1 mM after ingestion of either protein or water, confirming that ingested protein does not result in a net increase in glucose concentration, and results in only a modest increase in the rate of glucose disappearance.