Abstract: Abstract: Objective To investigate the effect of salidroside (SAL) on the proliferation and secretion of Toll-like receptor 4 (TRL4), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), osteoprotegerin (OPG) and receptor activator of NF-κB ligand (RANKL) in human periodontal ligament cells (hPDLCs) treated by lipopolysaccharide (LPS) and to provide preliminary experimental basis for treatment of periodontitis by salidroside. Methods hPDLCs were cultured by tissue cultivation in vitro and treated with 20 μg/mL LPS and various concentrations of salidroside for 12, 24 and 48 h. Cell proliferation of hPDLCs was detected by MTT assay. The expression levels of TRL4 TNF-α, IL-1β, IL-6, RANKL and OPG in hPDLCs were examined by Western blot, ELISA or qRT-PCR analysis. The data were processed by statistical analysis. Results Salidroside at low concentrations (≤10 μmol/L) significantly promoted hPDLCs proliferation in dose-dependent manner; 0.5 μmol/L of salidroside had the greatest effect whereas high concentrations of salidroside (>10 μmol/L) had no obvious effect on cell proliferation of hPDLCs; The expression of TLR4, TNF-α, IL-1β, IL-6 and RANKL was significantly increased by LPS stimulation. After treatment with 0.5 μmol/L of salidroside, the expression levels of TLR4, TNF-α, IL-1β, IL-6 and RANKL were significantly inhibited and the obvious effect occurred at 48 h (P＜0.05); In addition, the expression of OPG was nearly unchanged by LPS, but significantly upregulated by 0.5 μmol/L of salidroside. Conclusion Salidroside could attenuate LPS-induced cell injury in hPDLCs through inhibiting TLR4 signaling pathways and the production of inflammation factors including TNF-α, IL-1β, IL-6 and RANKL and promoting OPG expression which thereby inhibited inflammatory reaction and bone resorption.