To investigate the expression of galectin-1 with the stimulation of peritoneal dialysis solution (PDS) and its role in the epithelial-to-mesenchymal transition (EMT) in human peritoneal mesothelial cells (HPMCs). HPMCs were stimulated with PDS containing different concentrations of high glucose (1.5%, 2.5%, and 4.25%). After 24 h, mRNA and protein expressions of galectin-1,vimentin, and zo-1 were analyzed with real-time PCR and Western blot, respectively. Liposome transfected siRNA technique was used to knock down the expression of galectin-1 and the effect of galectin-1 siRNA on the EMT of HPMCs was also observed under 4.25% PDS condition. mRNA expression of galectin-1 in HPMCs increased in PDS groups, especially in group with 4.25% PDS (P<0.05). Protein expression of galectin-1 in HPMCs significantly increased in PDS groups with a dose dependent manner (P<0.05).Expression of vimentin in HPMCs significantly increased in PDS groups, especially in groups of 2.5% PDS and 4.25% PDS (P<0.05), but zo-1 expression markedly decreased (P<0.05). The expression of galectin-1 correlated positively with vimentin (P<0.05) but negatively with zo-1 (P<0.05). Expression of vimentin in groups of 4.25% PDS was markedly inhibited (P<0.05) by galectin-1 siRNA, whereas zo-1 expression was significantly increased (P<0.05). Galectin-1 can mediate high glucose PDS-induced EMT in HPMCs and may be a new target for the prevention and treatment of peritoneal fibrosis.