Ischemia/reperfusion (I/R) involves a cascade of reactions which ultimately lead to neuronal apoptosis or death. Inflammation plays an important role in this cascade. Chrysophanol (CHR), a purified active constituent from rhubarb, possesses many biological activities including anti-inflammation. The present study investigated the long-term neuroprotective effects of CHR on focal ischemic brain injury and the potential mechanism. Mice were subjected to 45-min middle cerebral artery occlusion and received either vehicle or CHR at 0.1, 1 or 10 mg/kg for 14 days after reperfusion. Neurological function, survival rate, brain tissue loss, expression of pro-inflammatory factors tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and nuclear factor-kappa B p65 (NF-kappa B p65) were then assessed. The results showed that treatment with CHR led to improved survival rate and reduced brain tissue loss compared with vehicle-treated mice, accompanied by improved neurological assessment and motor function, which were sustained for 14 days after I/R. I/R-induced expression of TNF-alpha, IL-1 beta and NF-kappa B p65 in neurons was markedly reduced in CHR-treated mice. These results indicate that CHR markedly attenuates brain injury after focal I/R, which is attributed at least in part to its anti-inflammatory actions. (C) 2016 Elsevier Ireland Ltd. All rights reserved.