Glucose is the major substrate that sustains normal brain function. When the brain glucose concentration approaches zero, glucose transport across the blood–brain barrier becomes rate limiting for metabolism during, for example, increased metabolic activity and hypoglycemia. Steady-state brain glucose concentrations in α-chloralose anesthetized rats were measured noninvasively as a function of plasma glucose. The relation between brain and plasma glucose was linear at 4.5 to 30 mmol/L plasma glucose, which is consistent with the reversible Michaelis–Menten model. When the model was fitted to the brain glucose measurements, the apparent Michaelis-Menten constant, K_t, was 3.3 ± 1.0 mmol/L, and the ratio of the maximal transport rate relative to CMR_glc, T_max/CMR_glc, was 2.7 ± 0.1. This K_t is comparable to the authors' previous human data, suggesting that glucose transport kinetics in humans and rats are similar. Cerebral blood flow (CBF) was simultaneously assessed and constant above 2 mmol/L plasma glucose at 73 ± 6 mL 100 g⁻¹ min⁻¹. Extrapolation of the reversible Michaelis–Menten model to hypoglycemia correctly predicted the plasma glucose concentration (2.1 ± 0.6 mmol/L) at which brain glucose concentrations approached zero. At this point, CBF increased sharply by 57% ± 22%, suggesting that brain glucose concentration is the signal that triggers defense mechanisms aimed at improving glucose delivery to the brain during hypoglycemia.