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However, the role of Rictor\/mTOR complex 2 (mTORC2) in regulating macrophage activation and kidney fibrosis remains largely unknown. We report here that Rictor\/mTORC2 was activated in macrophages from the fibrotic kidneys of mice. Ablation of Rictor in macrophages reduced kidney fibrosis, inflammatory cell accumulation, macrophage proliferation and polarization after unilateral ureter obstruction or ischaemia\/reperfusion injury. In bone marrow\u2010derived macrophages (BMMs), deletion of Rictor or blockade of protein kinase C\u03b1 inhibited cell migration. Additionally, deletion of Rictor or blockade of Akt abolished interleukin\u20104\u2010stimulated or transforming growth factor (TGF)\u2010\u03b21\u2010stimulated macrophage M2 polarization. Furthermore, deletion of Rictor downregulated TGF\u2010\u03b21\u2010stimulated upregulation of multiple profibrotic cytokines, including platelet\u2010derived growth factor, vascular endothelial growth factor and connective tissue growth factor, in BMMs. Conditioned medium from TGF\u2010\u03b21\u2010pretreated Rictor<jats:sup>\u2013\/\u2013<\/jats:sup> macrophages stimulated fibroblast activation less efficiently than that from TGF\u2010\u03b21\u2010pretreated Rictor<jats:sup>+\/+<\/jats:sup> macrophages. These results demonstrate that Rictor\/mTORC2 signalling can promote macrophage activation and kidney fibrosis. Targeting this signalling pathway in macrophages may shine light on ways to protect against kidney fibrosis in patients with chronic kidney diseases. Copyright \u00a9 2017 Pathological Society of Great Britain and Ireland. 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