This paper assesses the potential of ultrasonic desorption of toxic heavy metal Ni(II) from bentonite for regeneration purposes. Response surface methodology (RSM) was employed to optimize the desorption of Ni(II) retained on bentonite by varying the amount of adsorbent, contact time, pH and ultrasound time. The results indicated that in the present experimental setup, the pH and the ultrasound time were the most significant variables affecting Ni(II) desorption from bentonite. Based on statistical analysis, the Ni(II) desorption model was highly significant with very low p-values (<0.0001) and the optimal control parameters were determined as follows: solid/liquid ratio (0.5g/mL), contact time (6h), pH (3.37) and ultrasound time (30min). The experimental value of desorption percentage (59.4%) for regeneration of bentonite under the optimum conditions is in agreement with the predicted value of 64.5%.