This study was designed to investigate the effect of the administration of cadmium and nickel on the histology of the testes, sperm parameters, and the expression of CatSper 1 and CatSper 2 genes in adult male mice. Despite the vital role of CatSper genes in male fertility, very little is known about the factors that regulate their expression. Thirty-two adult male mice were randomly allocated into four groups. The control group received no treatment. The sham group was injected with normal saline. The cadmium and nickel groups were injected with 2 mg/kg/day of cadmium chloride or 5 mg/kg/day of nickel chloride for 2-weeks as models for testicular injury. Histological study and the analysis of their sperm were performed according to WHO’s guidelines for the examination of human sperm. In addition, a prooxidant antioxidant balance assay and real-time PCR were performed 35 days after the treatment, as the duration of spermatogenesis cycle in mice is 35 days. The data were analyzed using SPSS software using ANOVA. Both nickel and cadmium injections caused a reduction in sperm parameters as well as a decrease in the thickness of the germinal epithelium. The administration of cadmium caused down-regulation in the expression of both CatSper1 and CatSper2 genes. Only cadmium increased the PAB values.