Post-ischemic mild hypothermia is a robust neuroprotective agent for stroke therapy, but the complete mechanism of action is not yet fully understood. Therefore, as inflammation plays an important role in the ischemic cascade, the effect of hypothermia on pro- and anti-inflammatory cytokines was investigated. More specifically, changes in interleukin-1 beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha) and transforming growth factor beta (TGF-beta) respectively, were registered. In order to elicit a focal transient cerebral ischemic insult in male Wistar rats, endothelin-1 (Et-1), a potent vasoconstrictor, is infused adjacent to the middle cerebral artery. With this model, the core and the penumbra are represented respectively by the striatum and the cortex. Two hours of mild hypothermia (33°C), starting 20 minutes after the onset of the insult, is compared to normothermic (37°C) conditions. The levels of the cytokines are determined via ELISA in striatum and cortex, at 8 and 24 hours after administration of Et-1. Infarct size is assessed by cresylviolet staining. Twenty-four hours after the insult, mild hypothermia reduced the infarct size by half. Hypothermia significantly reduced the levels of IL-1beta in the penumbra, compared to normothermia, 24 hours after the insult. For TNF-alpha however, levels were increased 8 hours after the administration of Et-1 with the hypothermic treatment, in the core as well as in the penumbra. While at 24 hours, a significant decrease in the penumbra in TNF-alpha was seen. TGF-beta levels in the penumbra were not influenced by the hypothermic treatment. So, hypothermia has a significant effect on the pro-inflammatory cytokines but is without influence on TGF-beta.