A carbohydrate-rich diet induces glucose-phosphate dehydrogenase (GGPD) in liver parenchymal cells, which supports fatty acid synthesis de novo. Bacterial endotoxins stimulate GGPD expression in hepatic sinusoidal endothelial and Kupffer cells but not in parenchymal cells. This study was designed to elucidate whether GGPD expression is regulated uniformly by dietary carbohydrates in hepatic sinusoidal and parenchymal cells. Freshly isolated cells from five groups of Sprague-Dawley rats were analyzed for GGPD activity and mRNA abundance. The rats were grouped as follows: 1) food deprived for 24 h; 2) food deprived for 24 h followed by consumption of the standard diet for 48 h; 3) food deprived for 24 h followed by consumption of a carbohydrate-rich diet for 48 h; 4) fed standard diet; and 5) fed standard diet followed by consumption of a carbohydrate-rich diet for 48 h. In endothelial cells, GGPD activity was 150% greater in group 3 than in group 1 and 125% greater in group 5 than in group 4. Steady-state GGPD mRNA levels were elevated by 300% in endothelial cells from group 3 compared with those from group 1. In Kupffer cells, GGPD activity and mRNA abundance were not different among the groups. As expected, GGPD expression was 700-1200% greater in parenchymal cells from rats fed a carbohydrate diet (groups 3 and 5) than from controls. Our results indicate that short-term consumption of a carbohydrate-rich diet stimulates GGPD expression in endothelial and parenchymal cells. Because GGPD supports reactive oxygen metabolism, the response may represent a preconditioning of antioxidant pathways in the hepatic cell populations that are targets of sinusoid-born reactive oxygen species during infections.