Abstract: This experiment was conducted to study the promoting effect of IFN-γ on apoptosis of THP-1 cells infected with Mycobacterium bovis, and the role of TNF-α and its relevant signal molecules during cell apoptosis. IFN-γ (15 ng·mL^-1) was added to PMA differentiated THP-1 cells infected with M. bovis-BJ at different dose of MOI (10∶1, 20∶1), the percentage of apoptotic cells were analyzed by flow cytometry at 12, 24, 36, 48 and 72 h post infection. The results showed that IFN-γ promoted apoptosis of THP-1 cells infected with M. bovis was in a time-dependent manner. As incidence of apoptotic M. bovis–infected THP-1 cells treated with IFN-γ increased, the number of viable bacilli decreased. Anti-TNF-α monoclonal antibodies（3.0 μg·mL^-1, Mab）were added to THP-1 cells treated with IFN-γ and M. bovis (MOI, 10∶1), and the percentage of apoptotic cells and caspase-3, 8, 9 activity were determined at 36 h post infection. The results showed that the addition of anti-TNF-α Mab inhibited apoptosis of THP-1 cells treated with IFN-γ and M. bovis. A significant difference was found in the THP-1 cells treated with IFN-γ and M. bovis in the presence or absence of anti-TNF-α Mab (P<0.05), and that caspase-3 and caspase-8 were activated via a TNF-α dependent manner. THP-1 cells treated with IFN-γ and M. bovis-BJ were incubated for 36 hours in the presence of the following reagents: JNK inhibitor I or NEMO-Binding Domain (NBD) Binding Peptide alone, or the two inhibitors combined. No significant difference of THP-1 cells apoptosis in the presence or absence of the two inhibitors were observed (P＞0.05), indicating that JNK and NF-κB signal pathways are unlikely to be activated. This study elucidated that TNF-α associated in signal pathway of THP-1 cell apoptosis promoted by IFN-γ during early infection with Mycobacterium bovis.