Abstract: Objective To study the mechan ism s o f K_ATP channels protection on hippo campal neurons aga instapoptosis induced by chronic severe hypoxia.Methods The hypoxia inducible factor-1α(HIF-1α)expre ssion,DNA fraction,and cell apoptosis in control group,hypoxia group,hypoxia group treated with K_ATP channels antagonist and hypoxia group treated with K_ATP channels agonist were examined.Results After a 12 hours exposure to oxygen concentration of 0%,diazoxide (100 M),and K_ATP channels agonist,HIF-1α expression was increased and the hypoxic induced apoptosis was reduced.In contrast,to lbutamide(100 M),the K_ATP channels antagon istblocking the cellular sulphony lureas receptor,significantly rose the hypoxic induced apoptosis but down regulated HIF-1α expression.Conclusion K_ATP channels protect hippo campal neurons against chronic severe hypoxiavia down regulation of HIF-1α.