Objective: It has been known that the agents used in cancer treatment has acute toxic side effects on tissues with high proliferative activity. Although gonadal damage is widely seen, this side effect of anticancer agents has been studied less than other side effects. Therefore, this study was conducted to demostrate whether methotrexate (MTX) caused testicular toxicity associatead with the oxidative stress, and to investigate possible protective effect of chlorogenic acid against MIX-induced testicular damage. Material and Methods: Twenty four Wistar male rats were grouped into four as control, chlorogenic acid, MTX and chlorogenic acid+MIX (combined). The obtained tissue samples were examined via histological and biochemical methods. In each group 100 tubules were classified as intact, sloughing, atrophic or degenerated. Caspase 3 immunoreactivity was evaluated according to coloring magnitude as (+) weak, (++) mild and (+++) strong. Results: It was determined that in MIX group 43.5-24.2 of tubules were sloughing, 27.5-30.2 were atrophic and 1.0-2.0 were degenerated. In combined group, a effected tubule number was statistically smaller than MIX group. Coloring density and distribution of caspase 3 in MIX group was significantly greater. It was less in the combined group. Although malondialdehyde (MDA) increased in MIX group, catalese, superoxide dismutase and glutathion peroxidase values decreased compared to controls in biochemical analysis. In combined group, except MDA, the other parametres were similar to the control group. Conclusion: We suggest that an antioxidants like chlorogenic acid may be useful for decreasing the side effects of chemotherapy.