Objective To observe the effect of blood-cooling and blood-stasis-removing Decoction on anti-double-strain DNA ( anti-dsDNA) antibody, anti-nucleosome antibody ( AnuA) and serum levels of interleukin ( IL) -6, 17, 21 in spontaneous systemic lupus erythematosus ( SLE) MRL/lpr experimental rats. Methods The experimental rats were divided into blank control group, model group, and high- and low- dose Chinese medicine groups ( 25.2, 12.6 g/kg respectively) , the treatment lasting 8 weeks. At the end of the experiment, the blood taken from the orbital veins was separated for obtaining serum, and then the serum anti-dsDNA antibody, AnuA, IL-6,17,21 levels were tested by enzyme-linked immunosorbent assay ( ELISA). Results The serum autoantibody and IL-6, 17, 21 levels of rats in the model group were increased significantly as compared with the blank control group ( P<0.01). The serum antibody and cytokine levels of Chinese medicine groups were reduced as compared with the model group, the difference between high-dose Chinese medicine group and model group being significant ( P<0.01). Conclusion Blood-cooling and blood-stasis-removing Decoction has certain effect on reducing the serum levels of anti-dsDNA antibody, AnuA, and IL-6,17,21, which may coniribute to one of its therapeutic mechanisms for SLE.