We have previously shown that soy protein consumption improves lipoprotein concentrations and reduces the progression of atherosclerosis in cynomolgus monkeys. The mechanism for these beneficial effects is unclear. The purpose of this study was to determine potential mechanisms for the atheroprotective effects of soy and to determine if these effects extend to diabetic monkeys. We designed an experiment with a 2 x 2 factorial design in which adult male monkeys (N = 23) were fed an atherogenic diet with a protein source of either soy isolate or casein and lactalbumin, and the monkeys were either control or streptozotocin-induced diabetic. Diabetics had significantly increased fasting glucose and glycated hemoglobin (GHb) levels; this relationship was not affected by the type of dietary protein. Diabetics also had increased total (TC) and low-density lipoprotein cholesterol (LDLC) concentrations. However, soy consumption significantly reduced TC and LDLC concentrations in both control and diabetic monkeys. Plasma and arterial LDL metabolism was determined by injecting 125I-LDL at 48 hours and 131I-tyramine cellobiose LDL at 1 hour prior to necropsy. This allowed a determination of the arterial LDL concentration, permeability, and arterial LDL delivery. An increase in the whole-body plasma LDL fractional catabolic rate (FCR) was found with soy. Soy significantly reduced the arterial LDL concentration across all arterial sites by an average of 50%. Soy also significantly reduced the delivery of LDLC to all arterial sites by an average of 40%. While this was primarily due to the lower plasma LDLC concentration, LDL permeability in the carotid bifurcation and internal carotid arteries was also reduced. There was no additional effect of diabetes. These beneficial effects on plasma and arterial LDL metabolism would be expected to reduce atherosclerosis and were found in both control and diabetic monkeys.