Abstract: Objective To study the effect of obesity in pathogenesis of temporal lobe epilepsy. Methods A high-fat diet induced obesity model of C57BL/6J mice was established and then a normal dose of kainic acid （KA， 200 ng per mouse） were microinjected into the hippocampus of mice to induce temporal lobe epilepsy and seizures were scored with the Racine scores. The concentration of serum CK-MB was tested and the expression of S-100β was measured by Western blot. Then， the hippocampal pathogenesis of mice was observed 5 weeks after KA injection. Results The mean peak seizure scores of obese mice significantly increased compared with the wild mice after KA injection. After 24 h of injection of KA， the mean serum CK-MB concentration and hippocampal S-100βexpression of obese mice were higher than wild mice. The neuron loss and astrocyte activation significantly increased in hippocampal CA3 region of obese mice compared with these of the wild mice after KA injection， there were significantly morphologic change of reactive astrocyte in obese mice. Conclusion Obesity may be detrimental to KA-induced brain injury.