The LPS-induced mRNA expressions of pro-inflammatory markers were enhanced in the brains of sEH−/− mice. After intraperitoneal injections of LPS, the mRNA levels of GFAP and pro-inflammatory markers, including iNOS, COX-2, IL-6, and TNFα were evaluated in the hippocampus (a) and cortex (b) by qPCR. The data indicate that the basal levels of mRNA for all markers were comparable between wt (n = 9) and sEH−/− (n = 8) mice that received saline treatments. LPS treatments in Wt (n = 10) slightly increased the mRNA expression levels of GFAP and the pro-inflammatory markers in the examined brain regions except for iNOS in the cortex (p < 0.05), whereas LPS treatments in sEH−/− mice (n = 6) significantly increased iNOS (p < 0.01), IL-6 (p < 0.01), and TNFα (p < 0.001) in the hippocampus and GFAP (p < 0.01), COX-2(p < 0.05), IL-6 (p < 0.05), and TNFα (p < 0.05) in the cortex. Compared to Wt control with LPS, the mRNA levels of iNOS (p < 0.01), IL-6 (p < 0.01), and TNFα (p < 0.001) in the hippocampus were further enhanced in sEH−/− mice that received LPS. Similarly, significant increases of COX-2 (p < 0.05) and IL-6 (p < 0.05) in the cortex of sEH−/− mice with LPS were found. These data suggest that LPS treatments may result in higher mRNA expressions of some pro-inflammatory markers in the brain of sEH−/− mice than those in Wt. c The activity of sEH in the cortex and the hippocampus was lower in sEH−/− mice (n = 4, p < 0.001) than in wt mice (n = 5). A significant suppression of sEH activity was found in the hippocampus (p < 0.05) and cortex (p < 0.001) of Wt mice with LPS (n = 6). The activity of sEH in sEH−/− mice with LPS (n = 5) was slightly reduced, but not significant. Data are presented as the mean ± SEM. One-way ANOVA and Bonferroni multiple comparison test were performed. *p < 0.05; **p < 0.01; ***p < 0.001.