Therefore, these results demonstrate that inhibition of p38 activity prevents CdCl<sub>2</sub>-induced apoptotic GC-2spd cell death by reducing depolarization of mitochondrial membrane potential and mitochondrial ROS levels via ERK phosphorylation in a signal pathway different from the CdCl<sub>2</sub>-induced ERK/Drp1/p38 axis and suggest a therapeutic strategy for CdCl<sub>2</sub>-induced male infertility.