The hyperpolarization of neuronal membranes through the activation of potassium and chloride channels is a significant mechanism involved in the antinociceptive effects of various drugs. Thus, in this study, we aimed to determine whether potassium or chloride channels mediate the peripheral antinociceptive effects of epoxyeicosatrienoic acids (EETs). The mechanical paw pressure test was utilized as an algesimetric method. Hyperalgesia was induced by intraplantar injection of prostaglandin E2. The EETs (5,6-, 8,9-, 11,12-, and 14,15-EET) and the channel blockers were administered intraplantar in male Swiss mice (n=4). Statistical analysis was performed using ANOVA followed by Bonferroni post-test. Glibenclamide (Glib; 80 μg/paw), a blocker of ATP-sensitive K+ channels; tetraethylammonium (TEA; 30 μg/paw), a blocker of voltage-gated K+ channels; dequalinium (DQ; 50 μg/paw), a blocker of small conductance Ca2+ -activated K+ channels; and paxilline (Pax; 20 μg/paw), a blocker of high-conductance Ca2+-activated K+ channels, did not alter the peripheral antinociception induced by 5,6-, 8,9-, 11,12-, and 14,15-EET. All blockers, when administered alone, did not change the nociceptive threshold of the animals. Niflumic acid (Nifl. Ac.; 32 μg/paw), a selective calcium-activated chloride channels blocker, did not reverse the peripheral antinociceptive effect of 5,6-, 8,9-, 11,12-, and 14,15-EET. In conclusion, these results suggest that the peripheral antinociceptive effects of 5, 6-, 8,9-,11,12-, and 14,15-EET do not appear to be related to the opening of potassium or chloride channels.