Abstract Pattern recognition receptors (PRRs) play important roles in the inflammatory responses to Alzheimer's disease (AD). Our previous study indicated that soybean isoflavone (SIF) exhibited anti-inflammatory effect in rats treated by β-amyloid peptides1-42 (Aβ1-42). In present study, we further detected the effects of SIF against inflammation caused by Aβ1-42 treatment in rats. Serum inflammatory mediators and neurotrophic factors including transforming growth factor-β (TGF-β), inducible nitric oxide synthase (iNOS), brain-derived neurotrophic factor (BDNF) and S100β were detected by enzyme-like immunosorbent assay (ELISA). Reverse transcription-polymerase chain reaction (RT-PCR) and western blot methods were applied for detecting mRNA and protein expression of interleukin-1β (IL-1β), iNOS, tumor necrosis factor-α (TNF-α), TGF-β, BDNF, S100β, myeloid differentiation factor88 (Myd88), Toll-like receptor2 (TLR2), formyl peptide receptors (FPRs), inhibitor κB kinase (IKK) and inhibitor κB-α (IκB-α) in rat's brain tissue. Our results indicated that SIF could reduce the production of IL-1β, TNF-α and iNOS induced by Aβ1-42 in serum and brain of rats. SIF also significantly reversed Aβ1-42-induced up-regulation of TLR2, FPR, Myd88, IKK and decreased IκB-α mRNA and protein expressions in rats. These results suggested that TLR2 and FPR might involve in the inflammatory process induced by Aβ1-42 treatment, and SIF was an efficiency compound in reversing the inflammation caused by Aβ1-42 treatment.