Hedyotis corymbosa (Linn.) Lam. is a small herb commonly called as khetpapra, traditionally used to treat a wide range of diseases including abdominal pain, arthritis and inflammation. This study was conducted to evaluate the antinociceptive effect of ethanol extract of Hedyotis corymbosa (EEHC) whole plant.The antinociceptive activity of EEHC was evaluated in mice using both chemical- and heat-induced pain models such as acetic acid-induced writhing, hot plate, tail immersion, formalin, and glutamate tests at 50, 100, and 200mg/kg doses. In order to verify the possible involvement of opioid receptors in the central antinociceptive effect of EEHC, the effects found in hot plate and tail immersion tests were antagonized with naloxone.EEHC produced a dose-dependent antinociceptive effect against the chemical- and heat-induced pain in mice, significantly at 100 and 200mg/kg doses. These findings suggest that the action of EEHC involves both peripheral and central antinociceptive mechanisms. The antinociceptive activity of EEHC was significantly attenuated by pretreatment with naloxone, indicating the influence of opioid receptors on the exertion of EEHC action centrally.This study reports the antinociceptive activity of Hedyotis corymbosa and possible underlying mechanism(s) that supports the traditional use of this plant in the treatment of different painful conditions.