OBJECTIVE Accumulated evidence suggests that N(epsilon)-(carboxymethyl)lysine (CML), which is a dominant antigen of advanced glycation end-products (AGEs), is generated in the peritoneal cavity of patients undergoing continuous ambulatory peritoneal dialysis (CAPD), and that this process may be involved in the pathophysiology of the peritoneal injury found with CAPD treatment. Since CML is a sequential product of glycation and oxidation processes, CML generation could be suppressed by antioxidants. The aim of this in vitro study was to clarify the effect of N-acetylcysteine (NAC), an antioxidant, on CML generation from proteins under high glucose settings mimicking peritoneal dialysis solutions. DESIGN Test proteins (bovine serum albumin/type I collagen) were incubated continuously for 16 weeks in glucose solutions (200 mmol/L) with or without NAC (2 mmol/L), and the generation time courses (8 and 16 weeks) of CML and furosine (the biomarker of the glycation products of the early Maillard reaction) were determined. RESULTS In both proteins, furosine and CML were progressively generated in accordance with the duration of the incubation period. No apparent differences were found between solutions with and without NAC in furosine levels at the 8th and 16th weeks. However, the generation of CML was lower in the solution with NAC throughout the test periods. CONCLUSION The results showed that NAC could suppress the generation of CML. This indicates the therapeutic potential of antioxidants for the glycoxidative stress-related peritoneal injury occurring during CAPD.