The purpose of this study is to investigate the effect of decorin, a naturally occurring proteoglycan with anti-transforming growth factor beta (TGF-) activity, on the rat model of Peyronie's disease (PD). Twenty-five adult male Sprague-Dawley rats were divided in three groups: I) TGF- (0.5g) injected (n: 8); II) TGF- injected and decorin treated (n: 8); and III) controls (n: 9). Decorin (0.5g per day) was given with intracavernous injection on the second, third, fourth and fifth day following TGF- injection. All rats underwent electrical stimulation of the cavernous nerve after 6weeks. 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--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--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- in the rat model of PD and prevents diminished erectile response to cavernous nerve stimulation.