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Background: Urena sinuata L. is a wild shrubby plant with some folk medicinal use. To our knowledge, the biological importance of this plant has not been investigated yet. Purpose: The present study aimed to determine the neuropharmacology, antinociceptive, anti inflammatory and antipyretic effects of the chloroform extract of Urena sinuata leaves CEUS in rodents and to elucidate the possible mechanism of antinociception involved with its acute toxicity and phytochemical studies. Methods: Neuropharmacological activities of CEUS were conducted by hole cross, open field test, elevated plus maze test and thiopental induced sleeping time test. For the analgesic activity of CEUS different methods like hot plate test, acetic acid induced test, formalin induced test, tail immersion test and glutamate induced nociception were used. Additionally, the possible mechanism of nociception is identified by cyclic guanosine monophosphate and ATP sensitive K channel pathway analysis. Carrageenan induced rat paw edema and cotton pellet induced granuloma test also were used to detect anti inflammatory activity and brewers yeast induced pyrexia test for antipyretic activity. Results: The extract 200 and 400 mg/kg was administered orally 60min prior to subjection to the respective test. The results obtained demonstrated that CEUS produced significant neuropharmacological, anti inflammatory and antipyretic activity with low or no toxicity. The extract also exerts antinociceptive response in all the chemical and thermal-induced nociception models. Furthermore, it involves cyclic guanosine monophosphate and ATP sensitive K channel pathway mediated antinociceptive effect. Conclusions: These data show for the first time that CEUS has significant neuropharmacological, anti inflammatory and antipyretic effects which appear to be related to the inhibition of the glutamatergic system and rationalized the traditional use of the leaf in the treatment of different types of inflammation in intestines and bladder. Thus the leaves of Urena sinuata could be used in the treatment of several types of inflammation in intestines and bladder.