ABSTRACT Although tibial nerve modulation has shown to induce positive changes in the overactive bladder (OAB), prolonged therapeutic effects using percutaneous stimulation have not yet been achieved. Intradetrusor onabotulinum toxin A injection can provide prolonged therapeutic effects; however, its delivery requires invasive measures. By applying local relief of tibial nerve neural entrapment with onabotulinum toxin A injection, this study investigated the feasibility and efficacy of combining the abovementioned two therapeutic strategies. An OAB animal model was developed using 12 adult Sprague–Dawley rats with cyclophosphamide intraperitoneal injection. A perineural injection site comparable to the tibial nerve perineural injection site and corresponding to that in humans was identified and developed in rats. The toxin was injected five days after establishing the OAB. The incision was made in the skin on the lateral surface of the thigh. The biceps femoris muscle was cut across, exposing the sciatic nerve and its three terminal branches: the sural, common peroneal, and tibial nerves, and 100 units of onabotulinum toxin A was injected into the surrounding tissue. Five days following injection, cystometry was performed. Inter-contraction time, contraction pressure, and interval of the disease state improved with statistical significance. The OAB animal model showed significant improvement with the tibial nerve perineural injection of botulinum toxin, thereby suggesting the possibility of a comparable treatment adaptation in humans.