Abstract Background This study was conducted to investigate the therapeutic potential of the skin-derived precursor Schwann cells for the treatment of erectile dysfunction in a rat model of bilateral cavernous nerve injury. Results The skin-derived precursor Schwann cells-treatment significantly restored erectile functions, accelerated the recovery of endothelial and smooth muscle tissues in the penis, and promoted nerve repair. The expression of p-Smad2/3 decreased after the treatment, which indicated significantly reduced fibrosis in the corpus cavernosum. Conclusions Implantation of skin-derived precursor Schwann cells is an effective therapeutic strategy for treating erectile dysfunction induced by bilateral cavernous nerve injury.