Abstract: Sertoli cells from the testis contain immunoprotective properties which allow them to survive as allografts and also to protect islets and adrenal chromafin cells from immune rejection without the use of immunosuppressive drugs. Experiments were designed to determine whether xenogeneic neonatal porcine Sertoli cells (NPSCs) survive transplantation in rats without the use of immunosuppression. NPSCs (92.2 ± 5.1%) were isolated, cultured and then transplanted under the kidney capsule of non-immunosuppressed Lewis rats. To assess survival, grafts were removed after 4, 20, 30, 40, 60, and 90 days post-transplant and immunostained for the Sertoli cell marker vimentin. Survival was confirmed by polymerase chain reaction (PCR) for the porcine mitochondrial cytochrome oxidase II (COII) subunit gene, a marker for porcine tissue. In both methods, NPSCs were detected in the grafts for at least 90 days. Histologically, NPSCs were clustered in small aggregates or organized in tubule-like structures. When stained for the presence of proliferating cell nuclear antigen (PCNA), many Sertoli cells stained positive at 20 days post-transplant, indicating not only cell survival but also Sertoli cell proliferation. The number of PCNA postive cells decreased somewhat by 40 days with almost no positive Sertoli cells at 60 and 90 days. These data demonstrate that NPSCs survive long-term following xenotransplantation in rats, which to our knowledge is the first report of a discordant xenograft surviving without immunosuppression in a non-immunoprivileged site. Further study of the mechanism of NPSC xenograft survival may provide clues for promoting a local tolerogenic environment.