Microglial activation in response to physiological and pathological signals results in cell migration and processes rearrangement toward the site of tissue disturbances. among signals controlling microglia activation, CX3CL1 has the peculiarity of being expressed by neurons and bind to receptors (CX3CR1) only present on microglia. To migrate, microglial cells undergo changes in shape, involving ionic fluxes. We studied the stretch/swelling-activated currents, involved in cell migration in microglial cells from mouse hippocampal slices. The current was activated by a mild hypo-osmotic extracellular stimulus, causing time dependent increase in membrane conductance. This current was mainly due to chloride flux, as chloride substitution with impermeant ions like gluconate caused dramatic amplitude reduction and a shift in the reversal potential; and was abolished by typical inhibitors of stretch-activated current s, as flufenamic acid (200 ?M), IAA-94 (500 ?M) and DIDS (150 ?M). In addition, the same drugs reduced the speed of microglial process rearrangement in response to a localized ATP puff, indicating that hyposmotic stimulus activates a stretch-activated current involved in microglia rearrangement. We report that the application of CX3CL1, reduced the amplitude of stretch activated currents recorded in microglial cells suggesting a mechanism by which the chemokine expressed and released by neurons may intefere with microglial activation.