Objective: To explore the delayed neuroprotection induced by paeoniflorin(PF), the principal component of Paeoniae radix prescribed in Chinese medicine, and its underlying mechanisms in rats subjected to vascular dementia(VD). Methods: A rat model of VD was induced by bilateral common carotid arteries occlusion(BCCAO). Low-dose or high-dose PF(20 or 40 mg/kg once per day) was administrated for 28 days after VD. The behavioral analysis of rat was measured by water morris. Regional cerebral blood volume(r CBV), regional cerebral blood flow(r CBF) and mean transit time(MTT) were measured in the bilateral hippocampus by perfusion-weighted imaging(PWI). The levels of interleukin-1β(IL-1β), interleukin-6(IL-6), and tumor necrosis factor alpha(TNF-α) were measured by commercially available enzyme-linked immunosorbent assay kits. Protein levels were evaluated by western blot analysis. m RNA levels were evaluated by real time-polymerase chain reaction. Western blotting was used to estimate p65 translocation. Results: The behavioral analysis showed that PF could decrease the escape latency time(P<0.05), and increase the residence time of the original platform quadrant and the across platform frequency in water maze in VD rats(P<0.05). Likewise, PF remarkably promoted the r CBV(P<0.05), r CBF and decreased per minute MTT(P<0.05) in hippocampus of VD rats. Furthermore, PF decreased the release of IL-1β, IL-6 and TNF-α as well as inhibited the m RNA expression of IL-1β, IL-6 and TNF-α in the hippocampus of VD rats(P<0.05 or P<0.01). PF also could decrease the protein expressions of inducible nitric oxide synthase and cyclooxygenase-2 in the hippocampus of VD rats(P<0.05 or P<0.01). In addition, PF significantly inhibited the nuclear factor κB(NF-κB) pathway in the hippocampus of VD rats. Conclusions: PF significantly attenuates cognitive impairment, improves hippocampus perfusion and inhibits inflammatory response in VD rats. In addition, the anti-inflammatory effects of PF might be due to inhibiting the NF-κB pathway. PF may be a potential clinical application in improving VD. Objective: To explore the delayed neuroprotection induced by paeoniflorin (PF), the principal component of Paeoniae radix prescribed in Chinese medicine, and its underlying mechanisms in rats subjected to vascular dementia (VD). Methods: A rat model of VD was induced by bilateral Low-dose or high-dose PF (20 or 40 mg / kg once per day) was administered for 28 days after VD. The behavioral analysis of rat was measured by water morris. Regional cerebral blood volume (r CBV), regional cerebral blood flow (r CBF) and mean transit time (MTT) were measured in the bilateral hippocampus by perfusion-weighted imaging (PWI). The levels of interleukin-1β (IL- (IL-6), and tumor necrosis factor alpha (TNF-α) were measured by commercially available enzyme-linked immunosorbent assay kits. Protein levels were evaluated by western blot analysis. M RNA levels were evaluated by real time-polymerase chain reaction. Western blotting was used to estimate p Results: The behavioral analysis showed that PF could decrease the escape latency time (P <0.05), and increase the residence time of the original platform quadrant and the across platform frequency in water maze in VD rats (P <0.05). Furthermore, PF decreased the release of IL-1β, IL-6 and TNF-α (P <0.05) PF also could decrease the protein expressions of inducible nitric oxide synthase and cyclooxygenase (P <0.05 or P <0.01), as well as inhibiting the m RNA expression of IL-1β, IL-6 and TNF-α in the hippocampus of VD rats -2 in the hippocampus of VD rats (P <0.05 or P <0.01). In addition, PF significantly inhibited the nuclear factor κB (NF-κB) pathway in the hippocampus of VD rats. Conclusions: PF significantly attenuates cognitive impairment, improves hippocampus perfusion and inhibits inflammatory response in VD rats. In addition, the anti-inflammatory effects o f PF might be due to inhibiting the NF-κB pathway. PF may be a potential clinical application in improving VD.