To explore the effect and mechanism of Acori Tatarinowii Rhizoma-rehmanniae Radix Praeparata(ATR-RRP) herbal pair on learning and memory in a rat model of cognitive dysfunction and verify it through experiments.Methods:Potential targets for the treatment of cognitive dysfunction by ATR-RRP were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)，GeneCards，and Online Mendelian Inheritance in Man(OMIM).A protein-protein interaction(PPI) network was constructed，and common targets were subjected to Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis using the Database for Annotation，Visualization，and Integrated Discovery(DAVID) platform.Based on the results of network pharmacology prediction，animal experiments were conducted.The central nervous inflammation-induced cognitive dysfunction model was established by bilateral intracerebroventricular injection of lipopolysaccharide(LPS).The rats were continuously administered for 8 weeks，while the sham operation group was injected with an equal amount of saline.The Morris water maze was used to observe changes in spatial learning and memory in rats from each group.Enzyme-linked immunosorbent assay(ELISA) was used to detect the level of tumor necrosis factor-alpha(TNF-α) in rat serum，and Western blot was used to detect the expression of Toll-like receptor 4/nuclear factor-kappa B(TLR4/NF-κB) pathway-related proteins.Results:Twenty-six active ingredients were screened from ATR-RRP，targeting 64 disease-related targets，involving five main signaling pathways，i.e.，advanced glycation end products(AGE)-receptor for AGE(RAGE) signaling pathway，TNF signaling pathway，interleukin-17(IL-17) signaling pathway，TLR pathway，and NF-κB signaling pathway.The results of animal experiments showed that ATR-RRP at medium and high doses significantly shortened the escape latency of rats(P<0.05)，prolonged the time spent in the target quadrant(P<0.05)，and significantly reduced the expression level of TNF-α(P<0.05).ATR-RRP at low，medium，and high doses significantly reduced the expression of TLR4，p-NF-κB p65/NF-κB p65，and IL-6(P<0.05).Conclusion:ATR-RRP may intervene in the occurrence and development of cognitive dysfunction by reducing the release of inflammatory mediators through the TLR4/NF-κB pathway and inhibiting neuroinflammation，providing a direction for the development and application of effective components of this herbal pair against cognitive dysfunction.