Abstract： Objective： To investigate the effect of glycyrrhizin on brain injury of cerebral microvascular endothelial cells induced by hydrogen peroxide(H2O2) and its molecular mechanism. Methods： Rat cerebral microvascular endothelial cells (RCMECs) were treated with different concentrations of glycyrrhizin， and the cell activity was detected by Methylthiazolyl tetrazolium(MTT). RCMECs were injured by H2O2 and intervened with different concentrations of glycyrrhizin. Cell activity and apoptosis were detected by MTT and flow cytometry. The expressions of P21，Caspase-3 and PINK1 protein were detected by Western blot. The expressions of miR- 205 and PINK1 mRNA were detected by real-time fluorescence quantitative PCR (qPCR). miR- 205 was transfected into cells and treated with H2O2. The effects of overexpression of miR- 205 on the cell activity and apoptosis of RCMECs treated with H2O2 were observed. Results：There was no significant change in the survival rate of RCMECs treated with different concentrations of glycyrrhizin. H2O2 significantly decreased the survival rate and miR- 205 expression of RCMECs，and significantly increased the apoptosis rate，P21，Caspase-3 protein expression and PINK1 mRNA expression(P＜0.05). 2.5 μg/mL and 5.0μg/mL glycyrrhizin significantly increased the cell survival rate and miR- 205 expression of RCMECs treated with H2O2，and significantly decreased the apoptosis rate，P21，Caspase-3 protein level and PINK1 mRNA expression(P＜0.05). Overexpression of miR- 205 significantly increased the cell survival rate of RCMECs treated by H2O2，and significantly reduced the apoptosis rate and the expression of P21 and Caspase-3(P＜0.05). Inhibition of miR-205 or overexpression of PINK1 can reverse the promoting effect of glycyrrhizin on the activity of RCMECs after H2O2， and inhibit the inhibition of apoptosis， P21 and Caspase- 3 protein expression after H2O2. miR- 205 targets and regulates PINK1 expression. Conclusion： Glycyrrhizin can improve the activity of cerebral microvascular endothelial cells induced by H2O2 and inhibit its apoptosis by regulating the expression of miR-205/PINK1.