Objective:To inspect the relationship between the therapeutic effect of DHA on lupus nephritis and the negative immune regulation of TLR4/NF-κB signal pathway which was induced by SIGIRR;in vitro,to observe the effect of DHA on damaged HK-2 cell.Methods: In vivo,MRL/lpr mice were divided in model group,DHA groups(25,50,100 mg/kg),positive group (prednisone,5 mg/kg),and C57BL/6 mice were taken as control group.Administrate drugs daily for 12 weeks.Examine the changes in renal pathology;the expression of SIGIRR,IRAK1,TRAF6 in kidneys were determined by Western blot.In vitro,treat human renal tubular epithelial cell HK-2 cells with LPS ,and co-culture cells with DHA at the concentration of 0.67 μg/ml to 6.00 μg/ml for 6 h, 12 h and 24 h.Detect SIGIRR expression by Western blot and the level of IL-6 and CCL2 of HK-2 cells by ELISA.Results:In vivo, renal pathology revealed that kidneys of model group were damaged , while treatment with 100 mg/kg DHA alleviated renal injury.Compared to model group ,SIGIRR expression of DHA 100 mg/kg group increased a little ,and the expression of this protein had a tendency to increase with the augment of DHA dose .In vitro,DHA treatment reduced secretion of CCL 2 in HK-2 cells,and treatment of 0.67 μg/ml DHA for 24 h increased SIGIRR expression significantly , which also showed a growing expression with time.Conclusion:DHA could inhibit development of mouse lupus nephritis through increasing SIGIRR expression which inhibited TLR4/NF-κB signal pathway;DHA inhibited CCL2 secretion of HK-2 cells which were irritated by LPS ,and it may be associated with increased expression of SIGIRR .