The etiologies of erectile dysfunction (ED) after nerve‐sparing radical prostatectomy have not been clearly elucidated. The aim of this study was to evaluate the effects of cavernous nerve injury on cavernous fibrosis, and to consider measures to prevent irreversible damage to the cavernous tissues. Twenty male Sprague‐Dawley rats constituted the study population. The animals were divided into 2 groups; group 1 consisted of sham‐operated rats (n = 10), and group 2 consisted of rats that underwent incision of both cavernous nerves (n = 10). Three months later, all rats underwent intracavernous papaverine injection (300 and 600 mg), and intracorporal pressures were recorded. Transforming growth factor‐β₁ (TGF‐β₁) messenger RNA (mRNA) expression from rat penile tissue was measured using reverse transcriptase‐polymerase chain reaction. Hypoxia‐inducible factor‐1α (HIF‐1α), TGF‐β₁, and collagen I and III protein expressions were determined by Western blot analysis and immunohistochemical staining. Erectile function as studied with intracavernosal papaverine injection and histological analysis of penile cross‐sections at 3 months was similar in both groups. TGF‐β₁ mRNA expression, HIF‐1α, TGF‐β₁, and collagen I and III protein expressions were significantly greater in the neurotomy group. Immunohistochemical staining for TGF‐β₁, HIF‐1α, and collagen III were qualitatively more positive in the neurotomy group, whereas collagen I staining was similar. This study demonstrates an increase in TGF‐β₁, HIF‐1α, and collagen III synthesis in rat cavernosal smooth musculature after cavernous neurotomies. In theory, cavernous fibrosis may be reduced by employing various vasoactive agents or interventions that increase oxygenation to the corporal tissues during the postoperative period.