Objective To investigate the protective effects of curdione on cognitive and neurological function in mice with cerebral ischemia-reperfusion injury. Methods A middle cerebral artery occlusion mouse model was developed using middle cerebral artery embolization ( equivalent normal saline; model group; 20). Mice received the following treatments: low-molecular-weight heparin sodium [1 mg / ( kg·d); HS group; 20], low-dose curdione [20 mg / ( kg·d); CD-L group; 20] or high-dose curdione [ 60 mg / ( kg·d); CD-H group; 20]. We observed changes in behavioral evaluation, Morris water maze, cerebral infarction volume and cerebral water content, and measured the content of 6-keto prostaglandin F1α (6-keto PGF1α), thromboxane B2 (TXB2), 6-keto-PGF1α/ TXB2 in serum, and cAMP and p-CREB in brain homogenates. Results Compared with the sham operation group, the escape latency in the model group was significantly increased. Number of passes through the platform was obviously reduced (P< 0. 01). Behavioral evaluation, cerebral infarction volume, and content of cerebral water(%)and TXB2(pg / mL)were obviously increased. The content of 6-keto-PGF1α, 6-keto-PGF1α/ TXB2 ratios, cAMP and p-CREB were all significantly decreased (P< 0. 01). Compared with the model group, the escape latency in the CD-L and CD-H group was significantly decreased. The numbers of passing through the platform were obviously increased (P<0. 05). Behavioral evaluation, cerebral infarction volume, the content of cerebral water and TXB2 were obviously decreased. The content of 6-keto-PGF1α, 6-keto-PGF1α/ TXB2 ratios, cAMP and p-CREB were significantly decreased (P<0. 05), and appeared dose-dependent. Conclusions Curdione had a protective effect on cognitive function and neurological function in mice with cerebral ischemia-reperfusion injury. Its mechanism may be related to the reduction of TXB2, the increment of 6-keto-PGF1α, 6-keto-PGF1α/ TXB2 ratio, cAMP and p-CREB, thereby improving microcirculation disorders in cerebral ischemia reperfusion injury in a manner involving activation of the cAMP / CREB/ BDNF signaling pathway.