Heat shock proteins (HSPs) are evolutionarily conserved chaperones. Previously our group observed that overexpression of HSPB1 improved certain symptoms of Alzheimer’s disease (AD) in mice. The primary role of these chaperons is to maintain the protein homeostasis, however, several evidence suggest that they have additional functions, such as regulating inflammation. Therefore, our aim is to investigate the role of HSPB1 in chronic neuroinflammation and glia activation in a mouse model of AD.AD model (APP/PS1) mouse strain was crossed with an HSPB1 overexpressing line. Expression pattern of HSPB1 was studied using immunofluorescent staining. Neuroinflammation and glia activation in the hippocampus were studied by qPCR and immunohistochemical stainings.Due to a high incidence of seizures, female AD model mice show a higher mortality rate, which was remarkably reduced by HSPB1 overexpression. Immunofluorescent staining confirmed the accumulation of HSPB1 and the presence of activated glia cells around the Aß plaques. In the APP/PS1 group the expression levels of IL-1ß, IL-6, TNFα, astrocyte and microglia marker genes were significantly higher than those in wild-types. However, HSPB1 overexpression led to increased level of M2 anti-inflammatory microglia marker genes in APP/PS1 mice.Our results confirm that HSPB1 have protective effects against the symptoms of AD, which was demonstrated by the lower mortality rate observed in the APP/PS1/HSPB1 mice. Moreover, overexpression of HSPB1 may influence the activation of the microglia cells promoting tissue repair.This work was supported by NKFIH FK138390, ÚNKP-23-5 -SZTE-708 and the János Bolyai Research Fellowship of the Hungarian Academy of Sciences.