Moderate-intensity running (treadmill velocity of 21 m/min) increased blood lactate and actived transforming growth factor-β (TGF-β) concentration in rat cerebrospinal fluid (CSF). On the other hand, low-intensity running (15 m/min) did not increase blood lactate and caused no change in CSF TGF-β. Intraperitoneal (i.p.) administration of lactate to anesthetized rats caused an increase in blood lactate similar to that observed after a 21 m/min running exercise and increased the level of active TGF-β in CSF. Intraperitoneal administration of lactate at the same dose to awake and unrestricted rats caused a decrease in the respiratory exchange ratio, that is, enhancement of fatty acid oxidation and depression of spontaneous motor activity (SMA). Given that intracisternal administration of TGF-β to rats has been reported to enhance fatty acid metabolism and to depress SMA, we surmise that the observed changes caused by i.p. lactate administration in this study were mediated, at least in part, by TGF-β in the brain.