Puerarin　is　one　of　the　major　active　ingredients　in　Gegen,　a　traditional　Chinese　herb　that　has　been　reported　to　have　a　wide　variety　of　beneficial　pharmacology　functions.　Previous　studies　have　implicated　that　the　damaging　effects　of　hyperglycemia　resulting　from　oxidative　stress　and　glucose　fluctuation　may　be　more　dangerous　than　constant　high　glucose　in　the　development　of　diabetes-related　complications.　The　present　study　focuses　on　the　effects　of　puerarin　on　glucose　fluctuation-induced　oxidative　stress-induced　Schwann　cell　(SC)　apoptosis　in　vitro.　Primarily　cultured　SCs　were　exposed　to　different　conditions　and　the　effect　of　puerarin　on　cell　viability　was　determined　by　MTT　assays.　Intracellular　reactive　oxygen　species　(ROS)　generation　and　mitochondrial　transmembrane　potential　were　detected　by　flow　cytometry　analysis.　Apoptosis　was　confirmed　by　the　Annexin　V-FITC/PI　and　TUNEL　method.　Quantitative　real-time　reverse　transcriptase　polymerase　chain　reaction　was　performed　to　analyze　the　expression　levels　of　bax　and　bcl-2.　Western　blot　was　performed　to　analyze　the　expression　levels　of　some　important　transcription　factors　and　proteins.　The　results　showed　that　incubating　SCs　with　intermittent　high　glucose　for　48　h　decreased　cell　viability　and　increased　the　number　of　apoptotic　cells　whereas　treating　with　puerarin　protected　SCs　against　glucose　fluctuation-induced　cell　damage.　Further　study　demonstrated　that　puerarin　suppressed　activation　of　apoptosis-related　proteins　including　PARP　and　caspase-3,　downregulation　of　bcl-2,　and　upregulation　of　intracellular　distribution　of　bax　from　cytosol　to　mitochondria,　which　was　induced　by　glucose　fluctuation.　Moreover,　puerarin　inhibited　the　elevation　of　intracellular　ROS　and　mitochondrial　depolarization　induced　by　glucose　fluctuation.　These　results　suggest　that　puerarin　may　protect　SCs　against　glucose　fluctuation-induced　cell　injury　through　inhibiting　apoptosis　as　well　as　oxidative　stress.