<jats:title>ABSTRACT</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Neurogenic erectile dysfunction (ED) following radical prostatectomy (RP) is a frequent complication often leading to erectile tissue remodeling and permanent ED. Low-intensity electrostimulation (LIES) has been shown to enhance peripheral nerve regeneration, however, its application on cavernous nerves (CN) has never been investigated.</jats:p></jats:sec><jats:sec><jats:title>Aims</jats:title><jats:p>To investigate whether LIES enhances CN regeneration, improves erectile function (EF) recovery, and prevents corpora cavernosal remodeling after CN injury, which is a principal factor for ED following RP.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Adult male Sprague-Dawley rats were divided into Sham, Bilateral Cavernous Nerve Injury (BCNI), and BCNI + LIES (1V, 0.1ms, 12Hz, 1h/day). After 7days, EF was assessed (ICP measurement). Penes and CN were collected for molecular analyses of TGF-β1, Il-6, CRP, eNOS, ERK and AKT protein levels in corpus cavernosum (CC), and immunohistological analysis of DHE, total collagen and α-SMA in CC and S-100, Tub-III, DAPI, TUNEL, and nNOS in CN.</jats:p></jats:sec><jats:sec><jats:title>Outcomes</jats:title><jats:p>Effects of LIES on EF, erectile tissue remodeling and CN structure.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>EF was decreased (P &lt; .05) 7 days after BCNI and increased (P &lt; .05) by LIES. Intracavernosal reactive oxygen species (DHE) was increased (P &lt; .05) after BCNI and normalized by LIES. Protein expressions of TGF-β1, IL-6, and CRP were increased in the penis (P &lt; .05) after BCNI and normalized by LIES. The α-SMA and/or total collagen ratio was decreased (P &lt; .05) after BCNI in the penis and normalized by LIES. Protein expression ratio of p-ERK/ERK and p-AKT/AKT did not change after BCNI but increased (P &lt; .05) in LIES group. Myelination and number of nNOS positive cells in the CN were decreased (P &lt; .05) after BCNI and normalized by LIES. The number of apoptotic nerve cells within the dorsal penile nerve was increased (P &lt; .05) after BCNI and decreased (P &lt; .05) by LIES compared to the BCNI group. There were no differences in eNOS expression in the penis between study groups.</jats:p></jats:sec><jats:sec><jats:title>Clinical Translation</jats:title><jats:p>LIES may offer a potential new tool for penile rehabilitation and ED management following RP, potentially enhancing EF recovery and minimizing the side effects of this surgery.</jats:p></jats:sec><jats:sec><jats:title>Strengths & Limitations</jats:title><jats:p>This study provides evidence of the protective effect of LIES on EF and tissue remodeling following CN injury; nevertheless, this study has been conducted on animals and the translation to humans remains to be demonstrated. Further research to identify the underlying mechanisms of action is required.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>This study demonstrates that LIES of the CN after CN injury protects CN structure, enhances EF recovery, and prevents corpora cavernosal remodeling.</jats:p></jats:sec>