Background and Objective; Peroxisome proliferator-activated receptors gamma (PPAR款) agonist has been known to improve the insulin sensitivity, anti-inflammatory and anti-apoptotic effects. However, there are scare data about the relationship between PPAR款 agonist, Rosiglitazone (RSG), and anti-oxidant Thioredoxin (TRx) system in the cardiomyocytes (CMCs) under oxidative stress. We evaluated the effects of PPAR款 agonist, RSG, on CMCs under the H₂O₂-induced apoptosis and the patterns of TRx expression with or without inhibitors for TRx and PPAR款. Methods; Neonatal rat CMCs (rCMCs) were cultured from 2 day-old Sprague-Dawley rats. 1uM RSG or CMCs culture media as control was pretreated to rCMCs (3X10⁵ cells) before oxidative stress. Oxidative stress was induced by 0.5 mM of H₂O₂ for 4 hours. The proportion of apoptosis was measured by FACS with Annexin-V-PE staining with or without PX12 (inhibitor for TRx) and GW9662 (inhibitor for PPAR款) treatment. TRx system components including TRx, TRx interacting protein (TxNip) and TRx reductase (TRxR) and cell survival pathway (p-Akt /Akt, Bcl-2/Bax) were measured by Western blot analysis. Results: RSG effectively reduced H₂O₂ related rCMCs apoptosis compared to H₂O₂ control (10.99% vs 27.06%, difference 146%). Also, the expressions of TRx, p-Akt /Akt, Bcl-2/Bax were significantly increased in RSG group. However Txnip and TrxR expression was comparable between two groups. Px12 which are the chemical inhibitor of TRx limited the anti-apoptotic action of PPARr against H₂O₂- induced oxidative stress in rCMCs. Conclusion: RSG effectively protects rCMCs from apoptosis related with H₂O₂-induced oxidative stress. This phenomenon is closely related with RSG inducing TRx overexpression