In summary, we found that 1) pre-diabetes, induced by long-term high fat diet, increases expression of sEH mRNA and protein but not EETs levels in brain, 2) type 2 diabetes, induced by a combination of high fat diet and STZ/NA, exacerbates cerebral infarct size after MCAO in mice, and 3) sEH inhibition with t-AUCB, when administered prior to the ischemic event, improves glycemic status, increases cerebral perfusion, and reduces brain infarct size after MCAO. The gene discussed is EPHX2; the disease is brain infarction.