Abstract 【Aim】 The opening of the mitochondrial permeability transition pore (MPTP) leads to the changes of mitochondrial membrane permeability and is closely related to cell apoptosis. This study aims to explore the role of MPTP in the process of apoptosis induced by camptothecin (CPT) in Spodoptera exigua so as to further reveal the mechanisms of CPT-induced apoptosis in insects. 【Methods】 Effects of cyclosporine A (CsA), an inhibitor of MPTP, on the CPT-and 10-hydroxycamptothecin (HCPT)-induced apoptosis in IOZCAS-SPEX-Ⅱ cells of S. exigua were detected by flow cytometry. The detected parameters included the apoptosis ratio, intracellular Ca2+ concentration, mitochondrial membrane potential and reactive oxygen species (ROS), which would show the role of MPTP in the apoptosis induced by CPT and HCPT. 【Results】 After 10 μmol/L CPT and HCPT pre-treatment for 6 and 12 h, IOZCAS-SPEX-Ⅱ cells were apoptosized through a mitochondira-mediated pathway characterized by the increase of cytoplasmic Ca2+ concentration and ROS, and the reduced mitochondrial membrane potential in IOZCAS-SPEX-Ⅱ cells as compared with the control group (0.1% DMSO). However, after the pretreatment of 20 μmol/L CsA for 2 h, there were no significant differences between the control group of 0.1% DMSO and the CPT and HCPT treated groups (CsA+CPT or CsA+HCPT, 6 h) in the apoptosis ratio, cytoplasmic Ca2+ concentration, ROS generation, and the mitochondrial membrane potential, suggesting that CsA inhibited CPT- and HCPT-induced apoptosis by inhibiting MTPT open in IOZCAS-SPEX-Ⅱ cells. Interestingly, the inhibitory effects of CsA on MPTP were not detected after CPT and HCPT treatment for 12 h. 【Conclusion】 This study confirms that CPT- and HCPT-induced apoptosis in IOZCAS-SPEX-Ⅱ cells of S. exigua is through MPTP-dependent mitochondrial pathway during the initial several hours of treatment.