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Galanin is a neuropeptide with a widespread distribution throughout the nervous and endocrine systems, and recent studies have shown an anti-proliferative effect of galanin on several types of tumors. However, whether and how galanin and its receptors are involved in the regulation of cell proliferation in glioma cells remains unclear. In this study, the roles of galanin and its subtype 1 receptor (GAL1) in the proliferation of human U251 and T98G glioma cells were investigated. We found that galanin significantly suppressed the proliferation of U251 and T98G cells as well as tumor growth in nude mice. However, galanin did not exert apoptotic or cytotoxic effects on these two cell lines. In addition, we showed that galanin decreased the proliferation of U251 and T98G cells via its GAL1 receptor. Finally, we found that the GAL1 receptor was involved in the suppressive effects of galanin by activating ERK1/2.