Abstract： Objective To investigate the inhibition effect of Minocycline on hippocampal microglia in epileptic rats. Methods Forty male SD rats were equally randomized into normal saline control group (NS), penicillin inducement group, Minocycline post-treatment group and Minocycline pre-treatment group (n=10). Rat epilepsy models in the later 3 groups were induced by intraperitoneal injection of penicillin G at a dosage of 740 million to 7.6 million units/kg. The level of hippocampal microglia in rats of the 4 groups on the 1st and 3rd d of inducement was detected by immunofluorescence and the tumor growth factor-α (TNF-α) protein level was detected by Western blotting on the 1st and 3rd d of inducement. Results Seizure could activate microglia. As compared with those in rats of the penicillin inducement group, the activation and hyperplasia of microglia in the hippoeampus in rats of the minoeyeline post- and pre-treatment groups were obviously inhibited on the 1st and 3rd d of inducement (P≤0.05), and the effects were much obvious in the pretreatment group. The level of TNF-α protein in the penicillin inducement group, minoeycline post- and pre-treatment groups was significantly higher than that in the NS group on the 1st and 3rd d of inducement (P≤0.05); as compared with that in the penicillin inducement group, the level of TNF-α protein in the minocycline post- and pre-treatment groups decreased significantly on the 1st and 3rd of inducement (P≤0.05), especially that in the pretreatment group. Conclusion Minocycline can effectively inhibit the activation and hyperplasia of hippocampal microglia and the releasing of inflammatory factor TNF-αt in epileptic rats.