The ethanol extract of Achillea nobilis L. subsp. neilreichii (Kerner) Formanek (Asteraceae) flower heads was investigated for its antinociceptive and anti-inflammatory activities and for acute toxicity in mice and rats. While the extract exhibited an antinociceptive effect during the late phase of the formalin test (100, 200, and 400 mg/kg, i.p.) and an anti-inflammatory effect in the paw edema test (100 and 200 mg/kg, i.p.), it did not exert any significant antinociceptive effect in the tail-flick test. Furthermore, administration of 400 mg/kg extract increased the latency to hot-plate test at 60 and 90 min. No significant change was detected in sensory motor performance. The acute LC50 value of the extract was 4456 mg/kg (i.p.) in mice. The current results demonstrate that an ethanol extract of A. nobilis L. subsp. neilreichii exerts anti-inflammatory activity.