Objective To investigate the effects of sevoflurane on hypoxia-induced inflammatory responses of microglia and regulation of the nuclear factor erythroid 2-related factor 2 (NRF2) / heme oxygenase 1 (HO-1) / high mobility group protein B1 (HMGB1) pathway. Methods BV-2 mouse microglia were activated by inducing hypoxia for 0, 2, 4, 6, 8 and 12 h to establish an inflammation model. The activated cells were observed by inverted microscope, and the proportion of activated cells was calculated. Western blot were used to detect the expression levels of NRF2, HO-1, HMGB1 and interleukin (IL)-1β proteins in microglia. The optimal hypoxia time was 8 h. BV-2 microglia were activated under hypoxic conditions for 8 h; treated with different concentrations of sevoflurane (0%, 2%, 4% and 6%) for 30 min; and NRF2, HO-1, HMGB1, IL-1β protein expression was observed. BV-2 cells were divided into a control group, hypoxia- induction group, 6% sevoflurane group, SnPP group ( NRF2 / HO-1 pathway inhibitor stannous porphyrin), and 6% sevoflurane + SnPP group. The ratio of activated cells was calculated, and the protein expression levels of NRF2, HO-1, HMGB1, nuclear factor-κB p65 (NF-κB p65), phosphorylated NF-κB p65 (p-NF-κB p65) and IL-1β were determined. Results With prolonged hypoxia time, the proportion of activated cells and expression of HMGB1 and IL-1β gradually increased, and NRF2 and HO-1 proteins decreased to the lowest level at 8 ~ 12 h ( P< 0. 05). Therefore, the hypoxia- induction time of 8 h was chosen. With the increase in sevoflurane concentration, the proportion of activated cells and expression of HMGB1 and IL-1β gradually decreased, and NRF2 and HO-1 expression gradually increased (P< 0. 05). These effects were dose-dependent, and 6% sevoflurane was selected as the treatment concentration. Compared with that in the control group, the expression of NRF2 and HO-1 in the hypoxia-induced group decreased, and the proportion of activated cells and expression of HMGB1, IL-1β and p-NF-κB p65 / NF-κB p65 expression increased ( P< 0. 05). The changes in the above indices in the 6% sevoflurane group were opposite to those in the hypoxia-induced group (P<0. 05). The changes in the SnPP group were consistent with those in hypoxia-induced group and were more serious than those in hypoxia-induced group (P<0. 05). The changes in the above parameters in the 6% sevoflurane + SnPP group were opposite to those in 6% sevoflurane group ( P< 0. 05). Conclusions Sevoflurane treatment reduced hypoxia-induced microglial activation and inflammatory processes by promoting NRF2 / HO-1 activation and inhibiting HMGB1 expression.