〔Abstract〕 Objective To study the effect of lipopolysaccharide(LPS)-induced immune system activation on synaptic structure andDISC1gene expression in the cortex of rats with schizophrenia. Methods 40 rats were divided into 4 groups, which were PBS group, PBS+MK-801 group, LPS group and LPS+MK-801 group.The rats in LPS group and LPS+MK-801 group were administrated with LPS solution(0.2 mg/kg, i.p.BIW) for 6 times in total, the rats in PBS group and PBS+MK801 group were administrated with PBS.At the third time when the rats were administrated with LPS solution, the rats in PBS+MK-801 group and LPS+MK-801 group were administrated with MK-801 solution(0.5 mg/kg, i.p.BIW) for a total of 4 times, the rats in PBS group and LPS group were administrated with saline.The head shaking and the open field tests were then evaluated in the rats.Immediately, the rats were sacrificed, and their brain were saved for testing.RT-qPCR,Golgi staining, immunohistochemistry and ELISA kits were used to detectDISC1gene expression, dendritic spine status, microglia activation and inflammatory cytokine content in cortex, respectively. Results Compared with the PBS group, the expression ofDISC1gene of the rats in the PBS+MK-801 group increased(P<0.01),the score of head shaking increased(P<0.01),and the distance of the open field increased(P<0.000 1);As well as the LPS+MK-801 group, compared with the LPS group, the expression ofDISC1gene increased(P<0.000 1),the head shaking score and the distance of the open field increased(P<0.000 1).In addition, compared with the PBS+MK-801 group, the expression ofDISC1gene, the shaking head score and the open field distance of the LPS+MK-801 group further improved(P<0.000 1).Furthermore, compared with PBS group and PBS+MK-801 group, the content of iba1 in the cortex of LPS group and LPS+MK-801 group significantly increased(P<0.05),the content of inflammatory cytokines significantly increased(P<0.05),and the length and density of dendritic spines significantly decreased(P<0.05). Conclusion The activation of the immune system induced by LPS can contribute to the susceptibility of schizophrenia model, and the possible mechanism is that it cooperates with MK-801 to increase the expression ofDISC1gene, which ultimately leads to abnormal mental behavior in rats.