The regulatory peptide galanin is broadly distributed in the central- and peripheral nervous systems as well as in non-neuronal tissues, where it exerts its diverse physiological functions via three G-protein-coupled receptors (GAL1-3-R). Regulatory peptides are important mediators of the cross-communication between the nervous- and immune systems and have emerged as a focus of new therapeutics for a variety of inflammatory diseases. Studies on inflammatory animal models and immune cells revealed both pro- and anti-inflammatory functions of galanin. Here, we probed specific immune-related functions of the galanin system and found galanin and GAL1-R and GAL2-R mRNA to be expressed in a range of human immune cells. In particular, macrophages displayed differentiation- and polarization-dependent expression of galanin and its receptors. Exposure to exogenous galanin affected the cytokine/chemokine expression profile of macrophages differently, depending on their differentiation and polarization, and mainly modulated the expression of chemokines (CCL2, CCL3, CCL5 and CXCL8) and anti-inflammatory cytokines (TGF-β, IL-10 and IL-1Ra), especially in type-1 macrophages. Cytokine/chemokine expression levels in interferon-gamma- and lipopolysaccharide-polarized macrophages were upregulated whereas in unpolarized macrophages they were downregulated upon galanin treatment for 20 hours. This study illuminates the regulation of important cytokines/chemokines in macrophages by galanin, depending on specific cell activation.