We studied the effect of a krypton-oxygen mixture on the key signaling pathways associated with ischemic tolerance and suppression of secondary damage in a model of photoinduced stroke in male Wistar rats. In animals breathing the krypton-oxygen mixture, the expression of the transcription factor NF-κB (p50) in the brain was suppressed, indicating anti-inflammatory shifts in the brain tissue upon exposure to krypton, in parallel, increased content of phosphorylated forms of glycogen synthase kinase 3β (GSK-3β) and protein kinase B (Akt), components of the preconditioning cascade, was revealed. These results indicate a high potential of krypton in reducing acute cerebral disorders.