The antinociceptive effect of crude extract of Holarrhena floribunda T.Durand & Schinz together with its fractions prepared with hexane, chloroform, ethylacetate, butanol and aqueous were investigated using hot plate, tail immersion and acetic acid-induced abdominal constriction tests in mice. Acute toxicity studies were carried out on the crude extract and fractions by oral and intraperitoneal administration using Lorkes (1983) method. The crude extract was prepared by soaking the stem bark in 70% ethanol for 72 hours. It was filtered and evaporated using rota vapour. The dry crude extract was dissolved in distilled water followed by butanol, ethylacetate, hexane and chloroform in a separating funnel to obtained the fractions. The result shows that the crude extract and the fractions were not toxic with the exception of butanol fraction. The crude extract and the fractions shows dose independent significant increase in latency period in the hot plate and tail immersion tests. They also reduced the abdominal constriction induced by acetic acid in mice. The analgesic effect of the extract and fractions were reversed by naloxone an opioid receptor antagonist in the hot plate and tail immersion test; while naloxone did not reverse the inhibitory effect of the extract and fractions on the acetic acid-induced abdominal constriction test. The results show that the central analgesic effect of the crude extract and fraction is mediated through opioid receptor in the brain. The peripheral analgesic effect of the extract and fractions is not mediated through opioid receptors.