The purpose of this study was to determine the effects of in vivo atorvastatin, L-carnosine, and resistance exercise training on mitochondria-mediated apoptotic signaling in the rat skeletal muscle. Male Wistar rats were randomly assigned to control (CON), 5 mg atorvastatin treated group (STAT), 5 mg atorvastatin plus resistance (ladder climbing) exercise training group (STAT + EX), 5 mg atorvastatin plus L-carnosine treatment group (STAT + CAR), and 5 mg atorvastatin treatment plus resistance exercise training plus L-carnosine treatment group (STAT + EX + CAR) (n=12 rats/group). Animals were administered via oral gavage with a vehicle, 5 mg/kg/day atorvastatin, and 250 mg/kg/day L-carnosine dissolved in 0.25 % w/v hydroxypropyl methylcellulose for 12 weeks. Also, animals were trained for 12 weeks on a ladder with a gradient of about 80 degrees. Mitochondria-mediated apoptotic signaling (e.g., Bax, Bcl-2, mPTP opening, cytochrome c, cleaved caspase-3) were measured in skeletal muscles (e.g., soleus, white gastocnemius). Bax , pro-apoptotic protein, was increased in STAT in both soleus and white gastrocnemius and decreased in STAT + EX, STAT + CAR, and STAT + EX + CAR in both soleus and white gastrocnemius. In contrast, Bcl-2, anti-apoptotic protein, was elevated in STAT + EX, STAT + CAR, and STAT + EX + CAR in both soleus and white gastrocnemius and reduced in STAT in both soleus and white gastrocnemius. Also, mPTP opening, cytochrome c, and cleaved caspase-3 showed the same patterns like Bax in both soleus and white gastrocnemius. These data demonstrated that skeletal muscle mitochondria-mediated apoptotic signaling was impaired by atorvastatin treatment for 12 weeks. However, L-carnosine and resistance exercise training protected against statin-induced mitochondria-mediated apoptotic signaling in the rat skeletal muscle, suggesting that both L-carnosine and resistance exercise training play a pivotal role in ameliorating apoptosis in statin-induced myopathy.