Aim To investigate the effects of deferiprone (DFP) on expressions of iron transmembrane transport proteins concluding iron influx and efflux system in the hippocampus of cerebral ischemia-reperfusion rats. Methods The rats (n＝48) were randomly divided into sham operation group, cerebral ischemia-reperfusion group (I/R group) and DFP＋I/R group. All rats were pretreated by intragastric administration (ig) 1 h before the middle cerebral artery occlusion method for preparing cerebral ischemia-reperfusion model. After the operation, continuous ig administration was performed for days. After cerebral ischemia-reperfusion for 72 hours, the behavioral activity of rat was recorded by Longa's neurobehavioral score standard. Iron accumulation in the hippocampus was measured by DAB-intensified Perl's histochemical staining. Western blot was used to detect the expressions of iron transmembrane transport protein in hippocampus of rats in each group, including iron importin:transferrin receptor (TFR) and divalent metal ion transporter 1 (DMT1), iron exportin:ferroportin (Fpn), hephaestin (Heph), feline leukemia virus subgroup C receptor (FLVCR) and breast cancer resistance protein (BCRP). Results Compared with I/R group, the Longa's neurobehavioral score was significantly decreased (P＜0.01), the number of aggregated iron particles was reduced, the protein expressions of TFR and DMT1 were significantly decreased (P＜0.05 or P＜0.01), and the protein expressions of Heph, FLCVR and BCRP were up-regulated (P＜0.05 or P＜0.01), in the DFP＋I/R group. Conclusions Deferiprone can reduce the expressions of iron importin TFR and DMT1, increase the expressions of iron exportin Heph, FLVCR and BCRP, promote the efflux of heme iron and non-heme iron and reduce brain iron deposition. Thus it can decrease nerve damage after cerebral ischemia-reperfusion and improve the disease prognosis.