Epoxyeicosatrienoic acid (EET) has wide applications due to the unique biological effects of anti‑hyperlipidemia, inhibition of platelet aggregation, anti‑inflammation, anti‑cancer, anti‑lipid oxidation and the promotion of brain tissue development. The present study investigated whether EET ameliorates cerebral ischemia‑reperfusion injury (CIRI) by inhibiting inflammatory factors and pannexin. Specific pathogen‑free 7‑week‑old male Sprague‑Dawley rats were randomly divided into three groups: Sham, CIRI and EET. Neurological deficit scores, cerebral infarct volume and cerebral edema were assessed in CIRI rats. Enzyme‑linked immunosorbent assays were performed to detect tumor necrosis factor‑α, interleukin‑6, nuclear factor‑κB and inducible nitric oxide synthase (iNOS) levels, and western blot analysis was performed also used to assess cleaved caspase‑3, phospholipase A2 (PLA2), cyclooxygenase‑2 and prostaglandin E2 (PGE2) protein expression levels. EET ameliorated cerebral injury and CIRI‑induced cleaved caspase‑3 protein expression levels in rats. EET additionally suppressed CIRI‑induced inflammation reactions and iNOS protein expression in rats. Furthermore, the protein expression levels of PLA2, PGE2 and pannexin‑1 in CIRI rats were inhibited by treatment with EET. These results indicated that EET reduces CIRI by inhibiting inflammation and levels of cleaved caspase‑3, PLA2, PGE2 and pannexin-1.