This study aimed to assess the protective effects of Coenzyme Q10 (CoQ10) and propolis on paclitaxel (PTX)-induced cardiopulmonary toxicity. Thirty male albino rats were divided  into six equal groups. Group I (control), group II (CoQ10), group III (propolis), group IV (PTX), group  V  (CoQ10+  PTX)  and  group VI  (propolis+  PTX).  Intraperitoneal  injection  of  PTXinduced myocardial hyalinosis and necrosis associated with focal hemorrhages, swelling and damage of the endothelium lining the myocardial blood vessels with perivascular edema and mononuclear  cells  infiltration.  Also,  PTX  significantly  elevated  serum  CK-MB  and  LDH levels.  Furthermore,  PTX  causes  focal  hemorrhage,  perivascular  edema,  mononuclear  cell infiltrations and fibrinoid necrotizing vasculitis in the lungs with hyperplasia and desquamation of the bronchiolar epithelium. Strong positive immunoreactivity of TNF-α and low expression of Bcl-2 were recorded in the heart and lungs of rats in the PTX group. Pretreatment with propolis  or  CoQ10  markedly  improved  the  microscopic  pictures  of  the  heart  and  lungs confirmed by significantly mild immunoreaction of TNF-α and moderate expression of Bcl-2 in the  hearts and  lungs  and  reversed  the  elevated  CK-MB  and  LDH  levels.  In  conclusion, pretreatment with CoQ10 or propolis had a significant protective effect against PTX-induced cardiopulmonary toxicity through attenuation of proinflammatory cytokines and the apoptotic pathway.