AIM: To study the regulatory effect of nitric oxide on the lymphatic stomata and probe into the mechanism of ultrafiltration failure during long-term peritoneal dialysis (PD). METHODS: ①Sodium nitroprusside(SNP) and N G-monomethyl-L-arginine(L-NMMA) (inhibitor of nitric oxide synthase(NOS)) were injected into the peritoneal cavity of the mouse model of PD. ②NO concentration was measured in serum. ③The lymphatic stomata was studied with SEM and computer image processing.RESULTS: During PD, a lot of macrophages wandered out of the lymphatic stomata to form milky spots on the peritoneal mesothelium, and the diameter and density of the stomata were increased with NO concentration raised. After PD cessation, the stomata was normal gradually and numbers of milky spots reduced with NO concentration fall. The diameter and density of the stomata were increased with a rise in NO concentration as SNP was used, oppositely those were decreased with the increase in NO concentration as L-NMMA was injected intraperitoneally. CONCLUSIONS: The lymphatic stomata might be regulated through increasing the endogenous NO concentration. During PD, NO is increased gradually and the ultrafiltration failure would occur when re-absorption of the stomata was increased from the peritoneal cavity.