The application of D2EHPA in zinc solvent extraction has extensive background. To utilize more effectively, response surface methodology was used to optimize the concentration condition of zinc pregnant solution (ZPL) extracted by D2EHPA. In the current research, zinc, iron and manganese extraction along with separation factor of zinc-iron (Sf (Zn-Fe)) and zinc-manganese (Sf (Zn-Mn)) were considered as the response values. The optimal ZPL conditions extracted with 30% D2EHPA as the extraction solvent were as follows: Zn 21.96 g/L, Fe 382.57 ppm, Mn 1 g/L, Sf (Zn-Fe) 8.26 and Sf (Zn-Mn) 1529.82. In addition, it was found that the iron and manganese concentration were the most effective factors affecting the zinc and manganese extraction, respectively.