Aims: It has been long suspected that the cannabinoid system participates in the antinociceptive effects of nonsteroidal anti-inflammatory drugs. We studied the possible effects of cannabinoid receptor antagonism on diclofenac-induced antinociception in the writhing test in mice. Methods: In our study, male BALB/c mice, weighing 20-30 g, were used. Writhing responses were produced by intraperitoneal injection of 0.6% acetic acid. Different doses of diclofenac (3, 10, 30 mg/kg, i.p.) were tested, then the influence of AM-251 (1 mg/kg, i.p.), a cannabinoid CB1 receptor antagonist and AM-630 (3 mg/kg, i.p.), a cannabinoid CB2 receptor antagonist on the antinociceptive effects of diclofenac was studied. Results: Diclofenac administration elicited a significant, dose-dependent antinociceptive response; however, neither the cannabinoid CB1 receptor antagonist AM-251 nor the cannabinoid CB2 receptor antagonist AM-630 had any influence on the antinociceptive effect of diclofenac. Conclusion: Iinhibition of cannabinoid receptors does not contribute to the antinociceptive action of systemic diclofenac. Further studies are needed to explain the antinociceptive mechanism of diclofenac.