〔Abstract〕 Objective To investigate the improvement effect and possible mechanism of cornus officinalis glycosides on MRL/lpr lupus nephritis. Methods Forty mice lupus-prone MRL/lpr mice were divided into model group, cornus officinalis glycosides low-dose, medium-dose, high-dose group(27.5,55,110 mg/kg),with 10 mice in each group, and 10 C57BL/6 mice were taken as the control group.Gastric administration was carried out 1 time/day for 4 weeks.24-hour urine was collected before drug intervention and 2 and 4 weeks after intervention to determine the content of urine protein.After the drug intervention, mouse serum and kidney tissues were taken and the levels of serum creatinine(Scr),urea nitrogen(BUN) and anti-double-stranded DNA(dsDNA) antibodies were detected by kits.The levels of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β) in serum were detected by ELISA.The changes in peripheral blood T lymphocyte subsets were detected by Flow cytometry; The changes of renal histopathology were observed by HE staining; The protein expression levels of toll-like receptor 4(TLR4),myeloid differentiation factor-88(MyD88),nuclear transcription factor(NF-κB) p65,and p-NF-κB p65 in kidney tissue were detected by Western blotting. Results Compared with the control group, the changes of renal histopathology of the model group was severe, and the levels of 24-hour urine protein, Scr, BUN and anti-dsDNA antibodies, IL-1β,IL-6 and TNF-α significantly increased(P<0.01),the peripheral blood CD4+T/CD8+T lymphocyte ratio was significantly reduced(P<0.01),and the protein expression levels of TLR4,MyD88 and p-NF-κB p65 in kidney tissue were significantly up-regulated(P<0.01);Compared with the model group, the changes of renal histopathology of each dose group of cornus officinalis glycosides were significantly improved, the levels of 24-hour urine protein, Scr, BUN and anti-dsDNA antibodies, IL-1β,IL-6 and TNF-α were significantly reduced(P<0.01),the peripheral blood CD4+T/CD8+T lymphocyte ratio significantly increased(P<0.01),and the protein expression levels of TLR4,MyD88 and p-NF-κB p65 in renal tissue were significantly down-regulated(P<0.01).Among them, the high-dose group had the most significant changes in each index.While there was no significant difference in the expression of NF-κB p65 protein in the groups. Conclusion Cornus officinalis glycosides have a certain effect on renal inflammatory response in mice lupus-prone MRL/lpr mice, and the mechanism may be related to the inhibition of TLR4/NF-κB signaling pathway.