Macrophages are innate immune cells which undergo polarisation in response to different stimuli. Polarisation into a classical M1 phenotype in response to toll-like receptor ligands like lipopolysaccharide (LPS) or interferon γ (IFN-γ) can be distinguished from an alternative M2 activation after exposure to cytokines like interleukin 4 (IL-4) or macrophage colony-stimulating factor (M-CSF). It is well-known that polarisation towards M1 changes the expression pattern of ion channels in macrophages. The aim of the study was to investigate the expression pattern of ion channels in M2 polarised macrophages and to determine their function in the process of M2 polarisation. Bone marrow derived macrophages from C57Bl/6 mice were kept three days in culture and investigated after exposure to M1 (LPS 1 µg/ml + IFN-γ 10 ng/ml for 1 d) or M2 (IL-4 20 ng/ml or M-CSF 50 ng/ml for 3 d) stimuli. Ion channel activity in macrophages was investigated using the patch clamp technique. Proliferation, apoptosis and necrosis of macrophages was measured using fluorescent dyes binding to nucleic acids or caspases 3/7. Arginase activity was detected by conversion of arginine to urea and its subsequent reaction with a chromophore. Morphological changes were quantified by calculating an elongation factor. Cytokine release was measured using ELISA kits.Macrophages polarised with M2 stimuli expressed different K+, H+, Cl- and non-selective transient receptor potential (TRP) ion channels. In contrast to M1 macrophages, non-selective TRPM7 currents were 5-fold increased in M2 polarised macrophages. TRPM7 channel activity was completely inhibited by extracellular application of 50 µM NS8593 and 3 µM FTY-720. IL-4 and M-CSF increased the proliferation rates of macrophages 5- and 13-fold, respectively. This cytokine induced proliferation was abolished in the presence of TRPM7 inhibitors. The inhibition of proliferation was not caused by apoptosis or necrosis. IL-4, but not M-CSF induced a 79-fold increase in arginase activity, which was also partially reversed by TRPM7 inhibitors. Elongation of macrophages, a morphological change after exposure to M2 stimuli, was abolished in the presence of NS8593 or FTY-720. Furthermore, macrophages cultured with M2 cytokines like IL-4 released in the presence of TRPM7 inhibitors six times more tumor necrosis factor α in response to subsequent exposure to LPS than macrophages cultured with IL-4 alone.These data indicate that M1 and M2 macrophages have a distinctive expression pattern of ion channels. Most strikingly, M2 polarised macrophages exhibit significantly larger TRPM7 currents. This increased TRPM7 channel activity is necessary for macrophage proliferation and is involved in macrophage polarisation towards an M2 phenotype.