ObjectiveTo investigate the effect of Metformin (MET) on the anxiety behavior of mice with Pentylenetetrazol (PTZ)-induced epilepsy and the mechanisms. MethodsSixty male 8-week-old C57BL/6 mice were randomly divided into normal control group (Normal), Temporal lobe epilepsy (TLE) model control group (TLE-con), TLE + MET treatment group (TLE-MET), and normal mice + MET intervention group (MET-con) (n=15/group). In the TLE-con group and the TLE-MET group, mice were injected intraperitoneally with PTZ every other day to establish the TLE model, while mice in the Normal group and the MET group were given the same dose of normal saline. During PTZ administration, mice in the TLE-MET treatment group and the MET-con group were intraperitoneally injected with MET at 200 mg/(kg·d) every other day, for 14 times in a total of 28 days. The mice in the Normal group and the TLE-con group were intraperitoneally injected with the same amount of normal saline. Open field test (OFT) and elevated cross maze (EPM) were used to evaluate the anxiety behavior of mice in each group, and the Western blotting analysis was performed to detect expression of Toll like receptor 4 (TLR4), Nuclear factor-kappa B (NF-κB) p65 in brain tissues. ResultsCompared with the Normal group, the TLE-con group showed decreased times in the open arm in the EPM test (P<0.01) and in the center of open field in the OFT test (P<0.01), while MET intervention could increase the times of epileptic mice in the central area and the open arm (P<0.05). Compared with the Normal group, the expression of TLR4 and NF-κB in the cerebral cortex in the TLE-con group was increased significantly (P<0.05), while MET intervention could partially decrease the expression of TLR4 and NF-κB in the cerebral cortex of epileptic mice (P<0.05). ConclusionMET may improve the anxiety behavior of epileptic mice by reducing the inflammatory TLR4–NF-κB pathway.