Background: Apoptosis is one of the main means to remove undesirable cells that occurs in the eucaryotic and even procaryotic organisms. Objectives: This study aimed to examine the effect of 8 weeks of high-intensity interval training (HIIT) and crocin consumption on apoptotic factors in the soleus muscle of male rats exposed to doxorubicin. Methods: sixty male rats were selected and divided into five groups: 1) doxorbicin- control, 2) training, 3) crocin, 4) training + crocin, and 5) healthy control. Groups 1 to 4 received 2 mg/kg doxorubicin intraperitoneally; Groups 3 and 4 received daily 10 mg/kg crocin, and groups 2 and 5 received HIIT including high-intensity interval repetitions (80 to 90% of maximum speed) and low-intensity interval repetitions (30 to 40% of maximum speed) at two-minute alternations for eight weeks and for five days each week. Results: Doxorubicin had a significant effect on increasing Bax and caspase-3 and decreasing Bcl-2 (P ≤ 0.05). However, training had a significant effect on reducing Bax and increasing Bcl-2 (P ≤ 0.05). Crocin consumption had a significant effect on decreasing Bax and caspase-3 and increasing Bcl-2 (P ≤ 0.05). In addition, training and crocin consumption had interactive effects on decreasing Bax and increasing Bcl-2 (P ≤ 0.05). Conclusions: It appears that the combination of HIIT with crocin extract can be used to increase the expression of the Bcl-2 protein gene as an anti-apoptotic factor and decrease the expression of Bax gene as a stimulating factor in the soleus muscle of male rats exposed to doxorubicin.