The direct electrochemistry of epinephrine (EP) on a modified carbon paste electrode (CPE) was described. The electrode was modified with Zinc oxide (ZnO) nanoparticles and 1,3-dipropylimidazolium bromide as a binder. The oxidation peak potential of EP at the surface of the ionic liquid ZnO nanoparticle CPE (IL/ZnO/NP/CPE) appeared at 350 mV, which was about 80 mV lower than the oxidation peak potential at the surface of the traditional carbon CPE under a similar condition. On other hand, the oxidation peak current was increased for about three times at the surface of IL/ZnO/NP/CPE compared to CPE. The linear response range and detection limit were found to be 0.09–800 μmol L−1 and 0.06 μmol L−1, respectively. Other physiological species did not interfere in the determination of EP at the surface of the proposed sensor in the optimum condition. The proposed sensor was successfully applied for the determination of EP in real samples.