Summary: Diclofenac is a widely used non-steroidal anti-inflammatory drug whose analgesic, anti-inflammatory and antipyretic properties are used in the treatment of acute and chronic pain syndromes and inflammation. Its pharmacological activity extends widely beyond cyclooxygenase inhibition and includes novel multidirectional mechanisms of action. Experimental studies in vivo and in vitro have demonstrated the direct involvement of diclofenac in nociceptive processes by, among other things: effects on ion channels - potassium, sodium, calcium, acid-sensitive ion channels. Effects on NMDA receptors, TRP, thromboxane receptors have been documented. Diclofenac has been shown to have antinociceptive effects at the spinal level through activation of PPAR-γ and inhibition of prostaglandin synthesis and microglia activation, as well as effects on the NO - cGMP antinociceptive pathway, adrenergic and opioid systems. It has also been shown that diclofenac can affect the levels of endorphins and arachidonic acid, regulate the synthesis of interleukins and lipoxygenase. The above actions translate into diclofenac's direct involvement in nociceptive processes, with the end result of reducing the sensitivity of peripheral nociceptors and preventing sensitization. In addition, a number of potential applications of diclofenac have been demonstrated in neurodegenerative diseases and cancer, and the variety of novel mechanisms of action of diclofenac confirmed in experimental studies may suggest the potential for a relatively more favorable pleiotropic profile compared to other NSAIDs. However, the interactions exerted by diclofenac are not closed only within the beneficial actions, so further clinical studies are required to clarify the role of diclofenac in the mechanisms of nociception, as well as the possibility of implementing diclofenac in the treatment of neurodegenerative diseases and cancer and their accompanying pain syndromes.