Background : cyclophosphamide is an immunosuppressive agent and anticancer drug in childhood and adult malignant tumors . The compounds that have antioxidant properties might improve the side effect of cyclophosphamide on spermatogenesis. The aim of the work: This study designed to evaluate the effect of cyclophosphamide in testis of adult albino rats and the possible protective role of vitamin E and alpha lipoic acid . Materials and Methods: Forty male adult albino rats were divided equally into five groups Group I as a control group, Group II rats were given cyclophosphamide. Group III rats were given cyclophosphamide concomitantly with vitamin E. Group IV rats were given cyclophosphamide concomitantly with alph a lipoic acid. And Group V rats were given cyclophosphamide and a combination of vitamin E plus alph a lipoic acid. The testis samples were prepared for histological examination and PCNA immunohistochemical stain . Results: cyclophosphamide induced destruction of normal testicular histological structure, increased collagen fibers deposition and significantly decreased main area percent of PCNA immune -positive germ cells indicating decreased spermatogenesis. In group III vitamin E mild prevented the pathological changes in testicular tissue and non significantly increased the main area percent of PCNA immune -positive germ cells. While in group IV alpha lipoic acid enhanced marked preservation of the lined germinal cells and significantly increased the main area percent of PCNA immune -positive germ cells compared to group II. However, in group V there was almost total prevention of side effects induced by cyclophosphamide in adult rat testi s and preservation of spermatogenesis . Conclusion: Cyclophosphamid e induced damage in histological structure of testi s and decreased spermatogenesis of adult rats. Alpha lipoic acid comparatively preserved the normal histological structure of testis and normal spermatogenesis than vitamin E. However, administration of vitamin E and alph lipoic acid together was almost totally prevented the damaging effect of cyclophosphamid e .