Background: Previous studies found that transforming growth factor-β (TGF-β) induces mesothelial production of connective tissue growth factor (CTGF), which may be downstream mediators of TGF-β. Since high dose TGF-β induces apoptosis of peritoneal mesothelial cells (PMC), we study the effect of CTGF blockade in the system of TGF-β-induced PMC apoptosis. Method: We examined the effect of TGF-W in primary culture of rat peritoneal mesothelial cells (PMC). PMC apoptosis was studied by flow cytometry. The effect of CTGF was blocked by antibody and short-interfering RNA (siRNA). Expression of apoptotic gene was studied by real-time polymerase chain reaction. Result: In cultured unstimulated rat PMC, there is a low but definite incidence of spontaneous apoptosis. Stimulation with TGF-β 50 pg/ml induces an upregulation of apoptotic gene BAX expression and a downregulation of anti-apoptotic gene BCL-2L expression, and a 4-fold increase in PMC apoptosis. The effect of TGF-β-induced PMC apoptosis was partly prevented by antibody against CTGF, and completely abolished by CTGF-specific siRNA, while CTGF-blockade by siRNA had no effect on PMC necrosis. CTGF silencing by siRNA prevented the down-regulation of BCL-2L expression induced by TGF-β, had no effect on the BAX expression. Conclusion: Our results indicate that CTGF is an important downstream mediator of TGF-β-induced PMC apoptosis.