Nicotine is a member of the main constituents of tobacco smoke and the main cause of dysfunction in the body's organs is considered. The effects of nicotine on the cardiovascular system are well recognized. Thymoquinone (TQ), one of the components of the herb black seed oil, has anti- inflammatory and anti-cancer effects. This study was conducted to assess the ability of TQ against induced apoptosis by nicotine in heart tissue. For this purpose, thirty six male mice Balb/c were randomly divided into six groups: control, nicotine (5 mg/kg), TQ (9 and 18 mg/kg), nicotine + TQ (9 mg/kg) and nicotine + TQ (18 mg/kg) group. Bax and Bcl-2 gene expression in heart tissues were measured by quantitative real time PCR in all groups. Compare with control group, nicotine, TQ 9 and 18 mg/kg significantly increased the Bax/Bcl-2 ratio expression. Nicotine +TQ 9mg/kg administration did not induce any significant changes in the Bax/Bcl-2 ratio expression. In contrast, Nicotine +TQ 18mg/kg administration significantly decreased the Bax/Bcl-2 ratio expression compared to control group. Treatment with nicotine, TQ 9 and 18mg/kg induced the apoptosis in cardiac tissue by increasing the Bax/Bcl-2 ratio of expression. Pretreatment with TQ 18mg/kg to nicotine- treated mice inhibited the apoptosis in heart tissue and treatment of mice both dose 5 mg/kg nicotine and 9 mg/kg TQ did not lead to significant alterations in heart tissue. It can be concluded from this study that TQ exerts an anti apoptosis effect against nicotine- induced apoptosis.