In peritoneal dialysis (PD) therapy, physical stresses such as exposure to peritoneal dialysate, catheter trauma and peritonitis induce peritoneal injuries which can prevent continued long-term PD therapy. Therefore, protection of the peritoneum is an important target to enable long-term PD therapy in patients with end-stage renal disease. We previously showed that neutralizations of membrane complement regulators (CRegs), Crry and CD59, in rat peritoneum provokes development of acute peritoneal injuries due to uncontrolled complement activation. C5a is a key effecter molecule of the complement system, released during acute inflammation. Control of C5a has been proposed as a strategy to suppress inflammatory reactions and, because peritoneal injuries are accompanied by inflammation, we hypothesized that C5a targeted therapy might be an effective way to suppress peritoneal injuries. In the present study, we have used the established acute peritonitis model induced by neutralization of CRegs to investigate effects on acute peritoneal injuries of inhibiting C5a. Intravenous administration of an anti-C5a complementary peptide (AcPepA) up to 4 h after induction of injury significantly and dose-dependently prevented accumulation of inflammatory cells and reduced tissue damage in the model, accompanied by decreased C3b deposition. Here we showed that C5a contributed to the development of peritoneal injuries. Our results suggest that C5a is a target to prevent or treat peritoneal injuries in PD patients on prolonged therapy or with infectious complications.