〔Abstract〕 Objective To investigate the differential expression of LEFTY1 in peritoneal dialysis (PD)-associated peritoneal fibrosis (PF) and its clinical value. Methods Levels of LEFTY1, transforming growth factor-β (TGF-β), and fibronectin (FN) in peritoneal dialysis effluent were measured in 72 PD patients, and clinical data were collected. Differences in these indicators were compared among groups with different dialysis durations, and the correlation between LEFTY1 and clinical parameters was analyzed to evaluate its predictive value for ultrafiltration insufficiency. Results LEFTY1 levels decreased progressively with longer dialysis duration: short-term group [(2 262.49±270.47) ng/mL] > mid-term group [(1 853.52±226.06) ng/mL] > long-term group [(1 767.24±264.57) ng/mL], with significant differences among groups (P<0.001). TGF-β and FN levels increased with prolonged dialysis duration (P<0.05). Correlation analysis revealed that LEFTY1 was significantly negatively correlated with FN (r=-0.327, P=0.004), dialysis duration (r=-0.496,P<0.001), peritoneal Kt/V (r=-0.333, P=0.004), peritoneal creatinine clearance (r=-0.239, P=0.043), and serum calcium (r=-0.410, P<0.001), while positively correlated with total creatinine clearance (r=0.283, P=0.016). The area under the ROC curve for LEFTY1 combined with peritoneal Kt/V and peritoneal Ccr in predicting ultrafiltration insufficiency was 0.739. Multivariate regression analysis identified dialysis duration as an independent influencing factor for LEFTY1 expression (P=0.001). Conclusion The expression of LEFTY1 in the peritoneal dialysis effluent of PD patients decreases with prolonged dialysis duration and is negatively correlated with pro-fibrotic indicators, suggesting that it may play a potential anti-fibrotic role in the progression of PF. The combined detection of LEFTY1 and solute removal indicators holds value for the early identification of ultrafiltration dysfunction.