Abstract： Objective To research whether the inhibitory oligonucleotides could improve the immune status of the BXSB mice. The purpose was to provide a valuable direction for treating systemic lupus erythematosus. Methods 3-month-old BXSB lupus mice were divided into three groups (including inhibitory oligonucleotides group, saline group and blank control group). The 24 hours urine proteins were determined before treatment. After treatment,the urine protein, anti-dsDNA, peripheral blood lymphocytes apoptosis and immune complex in renal glomeruli were measured. Results Before treatment,the urine proteins had no statistical differences among the three groups ( P > 0.05 ).After treatment,the urine protein, anti-dsDNA levels in inhibitory oligonucleotides group were significantly lower than that of control group(P < 0.01 ). Apoptosis of peripheral blood lymphocytes in inhibitory oligonucleotides group was significantly higher than that of control group( P < 0.05 ) ,immune complex in renal glomeruli in inhibitory oligonucleotides group was significantly lower than that of the other groups ( P < 0.05 ). Compared with saline group, inhibitory oligonucleotides had prolonged life period of BXSB mice ( P < 0.01 ). Conclusion The inhibitory oligonucleotides could improve immune status of BXSB, and could put off the disease progression.