Changes in skin susceptibility and afferent pulsation frequency were measured in n. saphenous of rats undergoing the action of ultrahigh frequency electromagnetic radiation (UHF EMR). The study was aimed at verifying the hypothesis of the involvement of interleukine-6 (L-6) and endocannabinoids in the realization of the antinociceptive effect of UHF EMR. It was shown that UHF EMR with a wavelength of 7.1 mm lowers tactile, temperature, and pain sensitivity of the skin. This change was shown to correlate with the decreased electrical activity of afferent conductors of n. saphenous. Moreover, the IL-6 level in rat blood sera increased within 10 minutes after the irradiation both in the case of LPS-induced polyphasic fever in intact animals and under the normal conditions. This finding can possibly point out to the participation of this cytokine in the mechanisms of the antinociceptive effect especially in the case of pain of inflammatory origin. The data obtained give evidence that UHF EMR and anandamide exert a synergistic effect which confirms the involvement of the endocannabinoid system in the mechanisms of the antinociceptive action of the physical factor under consideration.