The consumption of soy protein was shown to reduce blood lipids in humans and other animal species. Furthermore, it was shown that the ingestion of soy protein maintains normal insulinemia. Thus, the purpose of the present study was to determine whether soy protein affects the synthesis of lipids in the liver through sterol-regulatory element binding protein-1 (SREBP-1) due to modulation of insulin levels. We first conducted a short-term study in which rats were fed a diet containing 18 g/100 g soy protein or casein for 10 d. Rats fed soy protein had significantly lower serum insulin concentrations than rats fed casein, and this response was accompanied by an elevation in hepatic SREBP-1 mRNA that was 53% lower than that in rats fed casein at d 10. The increase in SREBP-1 mRNA occurred 30 min after consumption of the casein mean, and increased steadily for the next 2 h. We then conducted a second study to assess the long-term effect of soy protein consumption for 150 d on hepatic SREBP-1 expression. Long-term consumption of soy protein maintained normal insulin concentrations compared with rats fed casein, which were hyperinsulinemic. Thus, rats fed the soy protein diet had significantly lower expression of SREBP-1 mRNA than rats fed the casein diet. Soy protein intake also reduced the expression of fatty acid synthase (FAS) and malic enzyme, leading to low hepatic lipid depots of triglycerides and cholesterol, whereas rats fed the casein diet developed fatty liver. These data suggest that soy protein regulates SREBP-1 expression by modulating serum insulin concentration, thus preventing the development of fatty liver.