Recent studies have shown that antibodies efficiently catalyze the conversion of molecular singlet oxygen (O) plus water to hydrogen peroxide (HO). HO is toxic to cells and is a cause of further free radical generation that are implicated in the pathogenesis of a variety of diseases. Systemic lupus erythematosus (SLE) is one of the most serious autoimmune diseases which are characterized by the production of various autoantibodies and subsequent tissue damage. However, the correlation of autoantibodies, HO, and tissue lesion in SLE has not been yet investigated. To address this issue, in the present study, we induced autoantibodies and kidney tissue damage by using SLE animal model as described previously. We detected the level of H O in SLE mice and found the increase of in vivo H O was accompanied and closely correlated with the production of anti-dsDNA and antihistone antibodies. Importantly, there was onefold increase of HO in the mice kidneys with apparent glomerulonephritis and IgG deposits. These results suggest that the induced autoantibodies possess catalytic activity. The produced autoantibodies lead to the production and elevation of HO, which results in subsequent renal damage and the pathogenesis of SLE. Our findings provide an insight into the understanding of SLE mechanism and provide a potential approach for therapeutic intervention of SLE. © Mary Ann Liebert, Inc.