In poorly controlled diabetics, the whole-body protein flux is increased by 20-30% in comparison to well-controlled type I diabetes (IDDM) and normal subjects. Intensive insulin administration completely reverses these abnormalities. In poorly controlled IDDM, the primary effect of insulin administration is to reduce the increased protein catabolic rate by suppressing the accelerated rate of protein breakdown. Studies in humans have demonstrated that the increased rate of protein synthesis observed in these patients is the consequence of elevated plasma amino acid levels. When IDDM subjects develop renal complications, a protein-restricted diet may be recommended to preserve the remnant kidney function. However, it has been demonstrated that in IDDM patients, metabolic adaptation to protein restriction is incomplete because suppression of endogenous proteolysis is impaired. Since this component of protein metabolism is very sensitive to insulin action, maintaining strict metabolic control during the protein restriction regimen has been suggested. The major studies on the effects of amino acid and insulin on protein metabolism in patients with diabetes mellitus are reviewed.