Extracts obtained from the seeds of Nigella sativa are used as a spice or remedy for the treatment of various inflammatory diseases. The purpose of this study was to examine the analgesic and anti-inflammatory effects of its polyphenols. N. sativa seed polyphenols were prepared, and analgesic and anti-inflammatory effects were studied in mice and rats using the acetic acid-induced writhing, formalin, light tail flick, carrageenan-induced paw edema, and croton oil-induced ear edema tests. In the acetic acid-induced writhing test, oral administration of N. sativa polyphenols (NSP) decreased the number of abdominal constrictions. Both oral and intraperitoneal administration of NSP significantly suppressed in a dose-dependent manner the nociceptive response in the early and late phases of the formalin test, and the effect on the late phase was more pronounced. Pretreatment with naloxone failed to reverse the analgesic activity of NSP in this test. NSP did not produce a significant analgesia in the light tail flick test in mice. Oral administration of NSP did not produce a significant reduction in carrageenan-induced paw edema. However, when injected intraperitoneally, NSP inhibited paw edema in a dosedependent manner. NSP when applied topically failed to reduce croton oil-induced ear edema. These results suggest that NSP have analgesic and anti-inflammatory effects. The lack of analgesic effect of NSP in the light tail flick test and also the failure of naloxone to reverse the analgesia in the formalin test reveal that mechanisms other than stimulation of opioid receptors are involved.