Microglia, macrophages of the CNS, remove particles via engulfment pseudopodia. We assume that formation and retraction of engulfment pseudopodia are due to localized volume regulatory processes. In global cellular volume regulatory processes Na⁺- and Cl^--conductance play major roles. Accordingly, we evaluated whether Na⁺ and Cl^- are involved in formation and retraction of engulfment pseudopodia. Primary BV-2-cells, a microglia cell line, have been exposed to polystyrenic microbeads (4 mm) for 15 minutes. Via scanning electron microscopy the number of engulfed beads under normal, Na⁺- or Cl^--free saline conditions as well as under exposure to the ENaC blocker Amiloride or Cl^--channel blockers (flufenamic acid, NPPB, DIDS, DIOA, DCPIB) was quantified. Na⁺- and Cl^--conductance was characterized using whole cell patch clamp recording. Cells bathed in Na⁺- or Cl^--free saline or in saline containing Cl^--channel blockers contained less engulfed beads than control cells. Addition of Amiloride, did not affect bead uptake. Electrophysiological experiments revealed swelling-activated Cl^--channels, which were sensitive to flufenamic acid, NPPB, DIOA, DCPIB. No Amiloride sensitive Na⁺-current was detected. Interestingly, cells exposed to beads for about one to five hours increased their swelling-activated Cl^--current by 106.71 %. Our study demonstrates that Cl^-- and Na⁺-conductances are necessary for formation of engulfment pseudopodia. The Cl^--conductance is related to swelling-activated Cl^--channels, whereas the identity of the Na⁺-conductance is unknown. Presumably, the up-regulation of the Cl^--conductance following engulfment of beads is pre-adaptation to handle the osmotic challenges due to degeneration of engulfed cell debris or pathogens.