Abstract Introduction A penile tunica defect may arise during penile prosthesis surgery or reconstruction of the penis in patients with Peyronie’s disease. Collagen fleece (TachoSil) was recently reported in penile surgery to cover the tunica defect with reported clinical success. However, it is not known what the histological outcomes of these grafts are in the penis. Objective We study the novel application of TachoSil graft in an experimental animal model. We looked at the regeneration of tunica albuginea, development of inflammation and fibrosis, and histopathological effect on the underlying cavernous tissue. Methods Seven adult male Sprague Dawley rats were used. All procedures were carried out under general inhalation anesthesia. The penis was degloved through a circumferential subcoronal incision. A longitudinal 1x10 mm defect was created at the base of the lateral aspect of the penis. A TachoSil patch (Takeda, Japan) was applied to the defect in six rats and Surgicel (Ethicon) in one. The penile skin covering is then restored and fixed with interrupted 5-6 zero absorbable sutures. At two months, the rat penis was evaluated for excision. Euthanasia was carried out with an overdose of inhalation anesthesia and chest opening. The excised penis was examined by hematoxylin and eosin and trichrome stains. Results At the time of surgery, the rats’ weight was 390 gm (SD 33.8). All rats with TachoSil showed normal-looking penis at two months with complete healing, no scaring, tethering, or gross inflammatory features. The penis of three rats with a Tachosil patch was harvested at two months postoperatively. It showed histopathology of fibrosis, chronic inflammation, and foreign body giant cell reaction at the site of the patch. There was no generation of a new tunica albuginea, no new vascularity or distinct fibrous layer development. The underlying corpus cavernous tissue was not affected by any inflammatory or pathological reaction. One rat died on the 6th postoperative day. Postmortem showed massive gastrointestinal bleeding, intraperitoneal hemorrhage, and punctate hemorrhages of the parenchyma of both suprarenal glands, both kidneys, and the liver. A clinical diagnosis of DIC was made. Histopathology of the penis, however, did not show micro thrombosis. The fifth rat with a Surgicel patch showed immediate hematoma of the penis controlled by compression. After two months, during harvesting of the penis, large pockets of pus were seen spreading from the site of the patch to surrounding structures. Histopathology showed chronic inflammation and fibrosis extending into the corpus cavernosum. The sixth and seventh rats showed normal penis external appearance at two months and were left surviving for harvest at four months. Conclusions Tachosil patching of penile tunica albuginea defect forms a distinctive barrier against inflammation protecting the underlying corpus cavernosum. However, no regeneration of tunica defect is observed at two months. DIC is a potential complication of systemic absorption of TachoSil. Disclosure No