To assess the distribution of cerebral cavernous malformation-2 (CCM2) and CCM3 proteins in a normal and experimentally induced varicocele model in rat testes. Comparative and controlled study. University animal care and operation unit. Wistar male rats for experimental and control groups. The control group underwent a sham operation. Rats in the experimental groups underwent partial ligation of the renal vein to induce experimental varicocele, and left testicular tissues were analyzed. Tissues were fixed and processed for paraffin-embedded testicular tissues. Levels of CCMs were assessed by immunohistochemistry and Western blot analysis. In control and sham-operated testes, CCM2 expression was detected in acrosomes of round spermatids at stages 6-8 and in the heads of elongating spermatids at stages 1-5 and 9-14. CCM3 expression was weakly localized in pachytene spermatocytes at stages 8-12 and strongly immunolocalized in the cytoplasm of round spermatids at stages 1-8 and in elongating spermatid cytoplasm at stages 9-12. Varicocele induction clearly demonstrated histopathological changes due to germ cell degeneration. CCM2 and CCM3 expression increased significantly in varicocele-induced rat testes. The expression patterns of two brain proteins were clearly identified in rat testes, suggesting a role during normal and pathological spermatogenesis. This article represents the first demonstration that these proteins have a role outside the central nervous system.