Objective To investigate the effects of baicalin on neuroinflammation and cognitive dysfunction in mice with cerebral ischemia-reperfusion injury （CIRI） by inhibiting PGE2. Methods Adult male C57BL/ 6J mice were randomly divided into two groups， the model of bilateral carotid artery occlusion （tBCCAO） was established. Baicalin was given by gavage or PGE2 was injected into lateral ventricle.The cognitive function of mice was detected by Morris water maze. The lipid peroxidation and neuroinflammation in hippocampus were measured by ELISA at 72 h after operation. The pathological changes of brain tissue were observed by HE staining. Western blot was used to detect the expression of GPX4， DMT1 and PTGS2 in hippocampus. Results CIRI induced cognitive impairment in mice， accompanied by hippocampal neuronal injury， neuroinflammation， lipid peroxidation and abnormal expression of ferroptosis associated proteins （P < 0.05）. Baicalin pretreatment could improve the cognitive impairment induced by CIRI in mice， and was accompanied by a reduction in hippocampal neuronal injury， neuroinflammation， lipid peroxidation and abnormal expression of ferroptosis associated proteins （P < 0.05）.PGE2 was upregulated in the hippocampus of mice after intracerebroventricular injection of PGE2， accompanied by neuroinflammation， lipid peroxidation and abnormal expression of ferroptosis associated proteins （P < 0.05）. Baicalin could decrease the neuroinflammation， lipid peroxidation and abnormal expression of ferroptosis associated proteins in hippocampus by inhibiting PGE2 up-regulation （P < 0.05）. The up-regulation of PGE2 in hippocampus aggravated the cognitive impairment induced by CIRI （P < 0.05）. Baicalin improved cognitive impairment by inhibiting the up-regulation of PGE2（P < 0.05）. Conclusion Baicalin ameliorates the cognitive impairment induced by CIRI， and the mechanism is related to the inhibition of PGE2-related neuroinflammation.