Purpose Increased TGF-beta 1 protein expression in tunica albuginea has been found to be associated with Peyronie's disease. The present study is designed to investigate whether surgical trauma induces TGF-beta up-regulation and histological changes in rat penis. Materials and Methods Thirty-two adult male Sprague-Dawley rats were divided into two groups. The first group (n = 24) underwent incision and suture repair of the tunica albuginea of the penis. The second group (n = 8) received sham surgery (incision of the penile skin and underlying fascia) as the control group. The trauma-induced group was divided into four subgroups in which the rats were euthanized at 6 hours (n = 6), 1 day (n = 6), 3 days (n = 6), and 8 weeks (n = 6). Two sham-operated (control) animals were also euthanized at each of the above time points. All tunical tissues from the trauma-induced and sham-operated rats were collected and examined histologically using Trichrome and Hart elastic fiber stain. Electron microscopy was used to study the ultrastructural changes of both trauma induced and control specimens. Western blotting technique was performed to study TGF-beta protein expression in both experimental and sham-operated groups. Results Tissue edema and hemorrhage between collagen bundles are noted in the experimental groups after 6 hours, 1 day and 3 days. At 8 weeks the most prominent changes observed were inflammatory cellular infiltration and disorganization of the collagen bundles. In the control group the tunica albuginea retains normal wavy regular appearance in all rats. This histological analysis is similar to the reported description of histological features of the acute phase of Peyronie's disease. Electron microscopy showed packed collagen bundles in the trauma-induced group with normal appearing elastic fibers. No abnormal change was detected in the control group. Immunoblot results revealed remarkable TGF-beta 1 protein expression in 1, 5, 3, and 0 rats of trauma induced subgroups after 6 hours, 1 day, 3 days, and 8 weeks respectively. No TGF-beta 1 protein expression in any rats in the control group was detected. No significant TGF-beta 2 or TGF-beta 3 protein expression was observed either in the trauma induced group or in the control group. Conclusion Trauma can induce histological changes similar to the acute phase of Peyronie's disease but not the overt picture of the chronic phase of Peyronie's disease. It can also result in an early but transient up-regulation of TGF-B1 protein expression in the rat penis. We conclude that surgical incisional trauma does not result in Peyronie's disease-like changes in the tunica.