Myocardial　infarction　(MI)　is　one　of　the　most　serious　cardiovascular　diseases　associated　with　myocardial　ischemia/reperfusion　(I/R)　injury.　Glaucocalyxin　A　(GLA)　is　a　biologically　active　ent-kauranoid　diterpenoid　that　has　been　found　to　ameliorate　myocardial　I/R　injury　in　mice.　However,　the　mechanism　has　not　been　fully　investigated.　In　the　present　study,　we　aimed　to　investigate　the　effect　of　GLA　on　rat　cardiomyocytes　H9c2　cells　exposed　to　hypoxia/reoxygenation　(H/R).　The　results　showed　that　GLA　treatment　improved　cell　viability　of　H/R-stimulated　H9c2　cells.　Administration　with　GLA　suppressed　the　H/R-stimulated　reactive　oxygen　species　(ROS)　production　in　H9c2　cells.　GLA　also　elevated　the　activities　of　antioxidant　enzymes,　including　superoxide　dismutase　and　glutathione　peroxidase　in　H/R-stimulated　H9c2　cells.　Moreover,　GLA　prevented　H/R-stimulated　cell　apoptosis　in　H9c2　cells,　as　evidenced　by　increased　bcl-2　expression,　decreased　bax　expression,　as　well　as　reduced　caspase-3　activity.　Furthermore,　GLA　enhanced　the　activation　of　protein　kinase　B　(Akt)/nuclear　factor　erythroid　2-related　factor　2　(Nrf2)/heme　oxygenase-1　(HO-1)　signaling　pathway　in　H9c2　cells　exposed　to　H/R.　Additionally,　treatment　with　LY294002　reserved　the　protective　effects　of　GLA　on　H/R-stimulated　oxidative　injury　in　H9c2　cells.　In　conclusion,　these　findings　suggested　that　GLA　protected　H9c2　cells　from　H/R-stimulated　oxidative　damage,　which　was　mediated　by　the　Akt/Nrf2/HO-1　signaling　pathway.　Thus,　GLA　might　be　a　promising　therapeutic　agent　for　the　prevention　and　treatment　of　myocardial　I/R.