Abstract: Background and Objective: Alzheimer's disease is a primary central degenerative disease, most of the current treatment drugs cannot delay or prevent the progression of the disease, only temporarily alleviating the symptoms. To investigate the mechanism of Jia Wei Kai Xin San on inhibiting the activation of microglia and realizing the anti-inflammatory effect by inhibiting the TLR4/MyD88/NF-κB signalling pathway in Alzheimer's disease rats. Materials and Methods: The rat model of AD was established by injecting Aβ1-42 into the lateral ventricle of the rat. Then, the rats were treated with different concentrations of Jia Wei Kai Xin San decoction by oral gavage for 6 weeks and the cognitive function and exploratory behaviour of the rats were measured. The expression levels of inflammatory factors in serum, cortex and hippocampus of the rats were detected by ELISA and Western blot and the pathological changes of the cerebral cortex were observed by HE staining. The co-expression of microglia markers in brain tissue was detected by the immunofluorescence double-label method. Results: All doses of Jia Wei Kai Xin San could improve the cognitive function and exploration behaviour of rats, inhibit the content of inflammatory factors in serum, cortex and hippocampus, alleviate the pathological changes of the cerebral cortex, inhibit the differentiation of microglia to M1-type and promote the polarization to M2-type. Conclusion: Jia Wei Kai Xin San could improve the cognitive function of Alzheimer's disease rats by decreasing the levels of inflammatory factors in serum and brain tissue, inhibiting the over-activation of TLR4/MyD88/NF-κB pathway in brain tissue and promoting the polarization of microglia into M2 type.