Objective To investigate the effect of silent information regulator 1 （SIRT1） on microglia in Status epilepticus （SE） and its mechanism. Methods The rat SE model was induced by lithium-pilocarpine injection. The activation of microglia in brain tissues of control and SE rats was observed by immunohistochemistry. Microglial activation model was established by lipopolysaccharide （LPS）. PcDNA-SIRT1 and si-SIRT1 vectors were constructed and transfected into rat microglia cells. The expression of SIRT1 in the rat hippocampus and microglia was determined by qRT-PCR. The expression levels of the activation markers of microglia （Iba1） and NF-κB p65 and IκBα were detected by Western blot， and levels of the inflammatory factors （IL-1β， IL-6 and TNF-α） were detected by ELISA. Results Comparing with the control group， the mRNA expression of SIRT1 in the hippocampus of SE rats was significantly decreased， while the protein expression of Iba1 was significantly increased. The number of Iba1 positive cells in CA1 and CA2 regions in the control group was （180±21） /mm2 and （190±18） /mm2 ， as （412±35） /mm2 and （470±37） /mm2 in the SE group. The difference in Iba1 positive cells in CA1 and CA2 regions between the two groups was statistically significant （P ＜ 0.05）. Similarly， the expression level of SIRT1 in LPS activated microglia was significantly decreased， while the expression level of Iba1 protein was significantly increased， with statistical significance （P ＜ 0.05）. pcDNA-SIRT1 and si-SIRT1 were transfected into the post-microglia cells activated by LPS. The levels of IL-1β （50.0±3.3） ng/L， IL-6 （55.0±3.2） ng/L and TNF-α （56.1±3.0）ng/L in LPS+pcDNA-SIRT1 were significantly lower than those in LPS group and LPS+pcDNA-NC group （P＜ 0.05）. The levels of IL-1β （98.2±4.3） ng/L， IL-6 （108.1±4.5） ng/L and TNF-α （124.5±4.1） ng/L in LPS+si-SIRT1 group were significantly higher than those in LPS group and LPS+si-NC group （P ＜ 0.05）. Besides， the NF-κB p65 expression in LPS+pcDNA·SIRT1 group was significantly lower than that in LPS group and LPS+pcDNA-NC group， while the IκBα expression was higher than those two groups （P ＜ 0.05）. However， the NF-κB p65 expression in LPS+si·SIRT1 group was significantly higher than that in LPS group and LPS+si-NC group， while the IκBα expression was lower than those two groups （P ＜ 0.05）. After giving the NF-κB pathway activator （Aconine）， compared with the LPS+pcDNA-SIRT1 group， the expression of Iba1 in the LPS+pcDNA-SIRT1+Aconine group was significantly increased （P＜ 0.05）. The expression levels of IL-1β were significantly higher in the LPS+pcDNA-SIRT1+Aconine group ［（72.2±4.3） ng/L， IL-6 （80.1±4.0） ng/L， and TNF-α （87.2±4.5） ng/L］ than that in the LPS + pcDNA-SIRT1 group ［IL-1β （50.1±2.3） ng/L， IL-6 （55.0±3.4） ng/L， and TNF-α （56.3±4.9） ng/L］ （P＜ 0.05）. Conclusions SIRT1 could inhibit the activation of microglia in SE rats by inhibiting the NF-κB pathway.