Type 2 diabetes increases CVD risk, however serum lipids in response to dietary change have not been fully investigated in adults with type 2 diabetes. This study determined the effect of soy protein isolate (SPI) on serum lipids in adults with type 2 diabetes. In a double-blind, randomized, crossover, placebo-controlled intervention study design, 29 adults with diet-controlled type 2 diabetes consumed SPI or milk protein isolate (MPI) for 57 days each separated by a 4-week washout. Fasted blood was collected on days 1 and 57 of each treatment and analyzed for serum lipids. SPI consumption significantly (p <=0.05) reduced LDL-C, LDL-C/HDL-C and apo B/apo A-I but did not significantly affect TC, HDL-C, TG, apo B or apo A-I, when compared with MPI consumption. These data demonstrate that consumption of soy protein can modulate serum lipids in a direction beneficial for CVD risk in adults with type 2 diabetes.