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Microglia play a defensive role by phagocytosing and clearing amyloid\u2010\u03b2 (A\u03b2) aggregates. However, excessive uptake of A\u03b2 leads to impairment of its clearing ability, which results in neuroinflammation and eventually neurodegeneration. Thus, enhancing microglial phagocytosis and reducing its pro\u2010inflammatory functions are promising strategies for AD therapy. However, harnessing microglial activation for long\u2010term benefits in controlling disease pathogenesis in AD is currently lacking. Our recent findings revealed that the astrocyte secreted cytokine Intercellular adhesion molecule 1 (ICAM\u20101) improves memory and cognitive impairments in a 5xFAD mouse model of AD. Here, we investigated the involvement of microglia in ICAM\u20101 function since its receptor, LFA\u20101, is expressed in microglia. We found that ICAM\u20101 blocks A\u03b2\u2010mediated microglial inflammatory activation by inhibiting the ERK\u2010STAT3 pathway, which is indispensable for microglial inflammation. Further, we found that ICAM\u20101 potentiates microglial phagocytic ability to eliminate A\u03b2 in primary culture. Additionally, ICAM\u20101 reduced A\u03b2 plaque load and associated microglial reactivation in the 5xFAD mouse hippocampus. This reduction in plaque\u2010associated microgliosis led to improved synaptic protein expressions which was reflected in significant cognitive improvement. Moreover, blocking the binding between ICAM\u20101 with its receptor LFA\u20101 partially reduced ICAM\u20101\u2010mediated microglial modification. 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