To determine the molecular events related to penile erection in the corpus cavernosum tissue of mice after electrical stimulation of the cavernous nerve. Twelve-week-old male C57BL/6 mice were used in this study. Electrical stimulation of the cavernous nerve was carried out to induce penile erection. Corpus cavernosum tissues were then harvested to determine the effect of nerve-induced penile erection on signaling pathway involved in angiogenesis (vascular endothelial growth factor, hepatocyte growth factor, angiopoietin-1, matrix metalloproteinase2, and matrix metalloproteinase9), cell survival and proliferation (phosphatidylinositol 3-kinase, phospho-Akt/Akt, and phospho-ERK/ERK), and tissue fibrosis (phospho-Smad2/Smad2, phospho-Smad3/Smad3, and plasminogen activator inhibitor-1). Cavernous nerve stimulation enhanced the expression of factors involved in angiogenesis (vascular endothelial growth factor, hepatocyte growth factor, angiopoietin-1, matrix metalloproteinase2, and metalloproteinase9), and activated intracellular signaling mediators related to cell survival and proliferation (phosphatidylinositol 3-kinase, phospho-Akt/Akt, and phospho-ERK/ERK), while suppressing the pathways involved in tissue fibrosis (phospho-Smad2/Smad2, phospho-Smad3/Smad3, and plasminogen activator inhibitor-1). Penile erection in mice is accompanied by the activation of a cascade of signaling pathways involved in angiogenesis, cell survival and proliferation, and antifibrosis. The present results might provide a theoretical and molecular basis for understanding the importance of penile rehabilitation and subsequent restoration of nocturnal or sexually-mediated penile erections.