The purpose of this study is to investigate the effect of decorin, a naturally occurring proteoglycan with anti-transforming growth factor beta (TGF-β) activity, on the rat model of Peyronie's disease (PD). Twenty-five adult male Sprague-Dawley rats were divided in three groups: I) TGF-β (0.5 μg) injected (n: 8); II) TGF-β injected and decorin treated (n: 8); and III) controls (n: 9). Decorin (0.5 μg per day) was given with intracavernous injection on the second, third, fourth and fifth day following TGF-β injection. All rats underwent electrical stimulation of the cavernous nerve after 6 weeks. Intracavernosal and arterial blood pressures were measured during this procedure. Cross-sections of the rat penises were examined using Mason trichrome and H&E stains. Statistical analyses were carried out using one-way anova. Histopathological examinations confirmed the Peyronie's-like condition in TGF-β-injected rats, which exhibited a thickening of the tunica albuginea (TA), when compared to controls. Disorganisation of collagen on the TA was also prominent in TGF-β-injected rats, but not in decorin-treated and control rats. Decorin-treated rats showed significantly higher maximal intracavernosal pressure (MIP) responses to cavernous nerve stimulation, when compared to group 1 (P < 0.05). Our results indicate that decorin antagonises the effects of TGF-β in the rat model of PD and prevents diminished erectile response to cavernous nerve stimulation.