Objective: To explore the roles of thrombospondin-1 (TSP-1) and transforming growth factor-β1 (TGF-β1) in mediating the secretion of extracellular matrix (ECM),such as fibronectin (FN) and collagen Ⅳ,from rat glomerular mesangial cell (GMC) induced by sublytic C5b-9 complexes. Methods: Rat GMC was cultured and divided into different groups. The expression levels of TSP-1 and TGF-β1 as well as FN and collagen Ⅳ in GMC with sublytic C5b-9 stimulation were measured. In addition,the synthetic blocking peptide of TSP-1(GGWSHW) and TGF-β1 neutralizing antibody were utilized to explore the role of TSP-1 and TGF-β1 in ECM secretion from GMC induced by sublytic C5b-9,as well as the relationship between TSP-1 and TGF-β1. Results: The protein levels of FN and collagen Ⅳ as well as TSP-1 and TGF-β1 including the activated TGF-β1 were significantly increased in rat GMC at 18 h after sublytic C5b-9 stimulation. The blocking peptides of TSP-1 (GGWSHW) could significantly inhibit TGF-β1 activation and reduce the production of FN and collagen Ⅳ. In addition,TGF-β1 neutralizing antibody could also obviously inhibit the expression of FN and collagen Ⅳ in GMC upon sublytic C5b-9 attack. Conclusion: Sublytic C5b-9 can promote ECM secretion and TSP-1 and TGF-β1 production as well as TGF-β1 activation in rat GMC in vitro,while the secretion of ECM stimulated by sublytic C5b-9 is possibly mediated in part by TSP-1-regulated TGF-β1 activation.