Introduction Cyclosporine A (CsA) has improved the quality of life and survival rate of transplant patients. However, the oxidative stress induced by CsA limits its use as it causes side effects in different organs. Lycopene is an antioxidant found in tomatoes, water melon, and pink guava. Aim of the work This study aimed to investigate the histological and immunohistochemical changes occurring in rat testes following CsA intake and evaluate the role of lycopene supplementation. Materials and methods Thirty adult male albino rats were divided into three groups: group I, group II, and group III. Group I was divided into subgroup IA, which received distilled water, and subgroup IB, which received lycopene (10 mg/kg/day) dissolved in corn oil. Group II received CsA (15 mg/kg/day) dissolved in distilled water and group III received CsA+lycopene at the same doses as above. All treatments were given by oral gavage for 21 successive days. Testis samples were prepared for light microscopic (histological and immunohistochemical) and electron microscopic examination. The area percentage of bcl-2 reaction and height of the germinal epithelium were morphometrically measured and statistically analyzed. Results The germinal epithelial cells of the CsA-treated group were separated and were seen to contain dark nuclei. Sloughed germ cells in the lumen were seen. Ultrastructurally, primary spermatocytes showed vacuoles. Spermatids had shrunken nuclei and irregular distribution of mitochondria. Leydig cells contained lipid droplets of different densities with projecting multiple processes. The basement membrane was thick and contained multiple collagen fibers. The axonemes of the mid-pieces of sperms were disorganized with swollen mitochondrial sheathes. Statistically, the area percentage of bcl-2 reaction and germinal epithelial height showed a significant decrease in group II versus other groups. Lycopene improved the adverse effects of CsA in group III. Conclusion CsA induced profound damage in the testicular structure in rats. It was ameliorated by concomitant lycopene administration. Thus, these results could be considered for further clinical investigations to recommend lycopene with CsA in transplant patients. Keywords: cyclosporineA toxicity, histology, immunohistochemisty, lycopene, oxidative stress, testis damage