Poststroke dementia commonly occurs following stroke, with its pathogenesis related to β-amyloid production and apoptosis. The present study evaluate the effects of paeonol, one of the phenolic phytochemicals isolated from the Chinese herb Paeonia suffruticosa Andrews (MC), on protection from memory loss after ischemic stroke in the subacute stage. Rats were subjected to transient middle cerebral artery occlusion (tMCAo) with 10 min of ischemia. The data revealed that paeonol recovered the step-through latency in the retrieval test seven days after tMCAo, but did not improve the neurological deficit induced by tMCAo. Levels of Amyloid precursor protein (APP)- and beta-site APP cleaving enzyme (BACE; β-secretase)-immunoreactive cells, and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL)-positive cells decreased in the paeonol-administered group. Western blotting revealed decreased levels of Bax protein in mitochondria and apoptosis-inducing factor (AIF) in cytosol following paeonol treatment. In conclusion, we speculate that paeonol protected memory after ischemic stroke via reducing APP, BACE, and apoptosis. Supression the level of Bax and blocking the release of AIF into cytosol might participate in the anti-apoptosis provided by paeonol.