Glia scar is a hallmark in late-stage of brain stroke disease, which hinder axonal regeneration and neuronal repair. Mitofusin2 (Mfn2) is a newly found cellular proliferation inhibitor. This study is to elucidate the role of Mfn2 in reactive astrocytes induced by oxygen-glucose deprivation/reoxygenation(OGD/R) model in vitro. Up-expression in EdU staining and protein level of GFAP, PCNA and CyclinD1, demonstrates the distinct activation and proliferation of astrocytes after the stimulation of OGD/R. Meanwhile, Mfn2 was proved to be down-regulated both in gene and protein levels. Pretreatment of cells with adenoviral vector encoding Mfn2 gene increased Mfn2 expression and subsequently attenuated OGD-induced astrocyte proliferation. Down-regulation of Ras-p-Raf1-p-ERK1/2 pathway and cell cycle arrest were found to be relevant. Together, these results suggested that overexpression of Mfn2 can effectively inhibit the proliferation of reactive astrogliosis, which might contribute to a promising therapeutic intervention in cerebral ischemic injury. (C) 2016 Elsevier Ireland Ltd. All rights reserved.