The invention discloses a complement receptor 2 variant, a fusion protein of the complement receptor 2 variant and a complement inhibitor and application of the fusion protein in preparing a medicament for treating autoimmune diseases. The complement receptor 2 variant is a molecular modified body obtained after computer modeling and amino acid replacement, has higher ligand binding and dissociation rate and better ligand binding force than a wild sequence of the complement receptor 2 variant. The biological distribution experiment proves that the fusion protein provided by the invention can rapidly and highly aggregate at an arthritis part after entering a rheumatoid arthritis mouse model, and has a remarkable anti-adhesion / anti-inflammation targeted inhibition effect. In the treatment ofMRL / lpr lupus erythematosus mice, the fusion protein can obviously improve the survival rate of the mice, and symptoms such as proteinuria, glomerular integral, interstitial inflammation, vasculitis,crescent / necrosis and the like of the mice in the treatment group are obviously improved.