Objective: To observe The effect of DHA on sevoflurane-induced TLR4/MyD88/NFκB pathway activation and the release of inflammatory mediators. Metheds Cells were assigned to Con group、Sevo group and DHA+Sevo group. After treated, cell suvival was assessed by MTT assay, Western blot were used to detect the expression of microglial TLR4、MyD88和IκB-α; then the contents of inflammatory mediator TNF-α、IL-1β和IL-6 in each group were detected. Results Compared with CON group, the survival rate of N9 cells in Sevo group decreased(P<0.05), and campared with Sevo group, the survival rate in DHA+Sevo group increased(P<0.05). Compared with CON group, the expression of TLR4 and MyD88 protein in microglia of Sevo group was up-regulated (P<0.05), and the expression of IκB-α protein was down-regulated (P<0.05). Compared with Sevo group, the expression of TLR4 and MyD88 protein in microglia of DHA+Sevo group was significantly down-regulated (P<0.05), and the expression of IκB-α protein was up-regulated (P<0.05). Compared with CON group and DHA group, the release of TNF-α and IL-1β from N9 microglial cells in Sevo group was increased (P<0.05). Compared with CON group, the release of TNF-α、IL-1β and IL-6 from N9 microglial cells in Sevo group was increased (P<0.05). Compared with Sevo group, TNF-α、IL-1β and IL-6 release was decreased in DHA+Sevo group (P < 0.05). Conclusion DHA alleviates TLR4/MyD88/NFκB pathway activation and inflammatory mediators release induced by sevoflurane.