To test the ability of huperzine B (HupB) to alleviate injury from oxygen-glucose deprivation (OGD) in the rat pheochromocytoma line PC12 cells.After OGD for 3 h and reoxygenation for 24 h, neuronal morphology was observed by phase-contrast microscopy; cell survival was quantified by the reduction of MTT; malondialdehyde (MDA) was determined by the thiobarbituric acid; superoxide dismutase (SOD) was assayed by a modification of the xanthine/xanthine oxidase; and lactate (LA) was measured according to Marbach and Weil.OGD for 3 h and reoxygenation for 24 h triggered death in nearly 70 % of cells, along with major changes in morphology and biochemistry including elevated level of MDA, SOD activity, and LA content. Cells pretreated with HupB 1-100 micromol/L for 2 h showed significantly improved survival and reduced biochemical and morphologic signs of toxicity.HupB protected PC12 cells against OGD-induced injury, most likely by alleviating disturbances of oxidative and energy metabolism.