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&NA; This study aimed to investigate the effect of sulfated polysaccharide from red seaweed Solieria filiformis (Fraction F II) in the inflammatory hypernociception in the temporomandibular joint (TMJ) of rats. Male Wistar rats were pretreated (30 min) with a subcutaneous injection (s.c.) of vehicle or FII (0.03, 0.3 or 3.0 mg/kg) followed by intra‐TMJ injection of 1.5% Formalin or 5‐hydroxytryptamine (5‐HT, 225 &mgr;g/TMJ). In other set of experiments rats were pretreated (15 min) with an intrathecal injection of the non‐selective opioid receptors Naloxone, or &mgr;‐opioid receptor antagonist CTOP, or &dgr;‐opioid receptor Naltridole hydrochloride, or &kgr;‐opioid receptor antagonist Nor‐Binaltorphimine (Nor‐BNI) followed by injection of FII (s.c.). After 30 min, the animals were treated with an intra‐TMJ injection of 1.5% formalin. After TMJ treatment, behavioral nociception response was evaluated for a 45‐min observation period, animals were terminally anesthetized and periarticular tissue, trigeminal ganglion and subnucleus caudalis (SC) were collected plasma extravasation and ELISA analysis. Pretreatment with F II significantly reduced formalin‐ and serotonin‐induced TMJ nociception, inhibit the plasma extravasation and inflammatory cytokines release induced by 1.5% formalin in the TMJ. Pretreatment with intrathecal injection of Naloxone, CTOP, Naltridole or Nor‐BNI blocked the antinociceptive effect of F II in the 1.5% formalin‐induced TMJ nociception. In addition, F II was able to significantly increase the &bgr;‐endorphin release in the subnucleus caudalis. The results suggest that F II has a potential antinociceptive and anti‐inflammatory effect in the TMJ mediated by activation of opioid receptors in the subnucleus caudalis and inhibition of the release of inflammatory mediators in the periarticular tissue. HighlightsF II has antinociceptive and anti‐inflammatory effect in the TMJ.F II inhibits the release of inflammatory cytokines IL‐1&bgr; and TNF‐&agr;.F II increases the &bgr;‐endorphin release in the subnucleus caudalis.The antinociceptive effect of F II depends on the opioid receptors mu, delta e kappa.