Objective: It is well documented that an imbalance in immune tolerance at the maternal-fetal interface is likely to play an essential role in the etiology of preeclampsia. However, the mechanisms underlying immune tolerance during preeclampsia are still poorly understood. Tim-3, a Th1-specific cell surface molecule, is a relatively newly described molecule with important immunological functions. It can regulate Th1 responses with its ligand galectin-9 (Gal-9), and has become an attractive candidate for exploring the pathogenesis of preeclampsia. Study design: Twenty normal pregnancies and 20 preeclamptic pregnancies were enrolled in the present study. We examined the expression and function of Tim-3/Gal-9 in decidual tissue at the RNA and protein levels. In order to analyze their correlation with the development of preeclampsia, we measured the expression of Tim-3 on peripheral blood leukocytes using flow cytometry. IFN-gamma, IL-10, and IL-17 in the peripheral blood plasma were measured by ELISA. Results: Tim-3/Gal-9 was upregulated in decidual tissue of preeclamptic vs. normotensive pregnancies. There was a significantly increased Th1 and Th17 response in PE as demonstrated by the upregulated levels of IFN-gamma/IL-17, whereas IL-10 secreted by Th2 cells was sharply reduced. Conclusions: The present study showed that an abnormal Tim-3/Gal-9 pathway was able to facilitate the development of preeclampsia. Our data uncovered a novel mechanism by which the Tim-3/Gal-9 pathway regulates immune responses, and we now identify this pathway as a potential therapeutic target in preeclampsia. (C) 2015 Elsevier Ireland Ltd. All rights reserved.