Barleria prionitis Linn.(Acanthaceae) is a prickly shrub and traditionally whole plant is used as anti-inflammatory, expectorant, analgesic, diuretic, antirheumaticand antidiabetic. This study was conducted to investigate the antinociceptive and CNS depressant activity of ethanolic extract and the fractions of B. prionitis in mice. Ethanol extract and its fractions were tested at a dose of 200 and 400 mg/kg. Ethanol, petroleum ether and chloroform fractions demonstrated significant antinociceptive activity at 400 mg/kg and significantly increased the latency in hot plate test and the action was antagonised by naloxone, indicating a potential opioid-like mechanism. In conclusion, the ethanol, pet ether and chloroform fractions of B. prionitis markedly demonstrated the antinociceptive action. The CNS depressant and good protective effect on pain stimuli suggest that the possible mechanisms appear to be due to involvement of opioid and/or peripheral receptors.