The leaf of Nymphaea lotus has been used traditionally for the management of pain and inflammatory diseases. The methanol leaf extract of Nymphaea lotus (NLE) was evaluated for possible anti-nociceptive and anti-inflammatory activities in rats and mice (at the doses of 250, 500 and 1,000 mg/kg) to investigate the existence of scientific basis for the folkloric use of the plant. The standard drugs used were piroxicam (10 mg/kg) and morphine (10 mg/kg). The possible pharmacological mechanism involved in the anti-nociceptive activity was also investigated. The acute toxicity was determined in mice and rats using method of Lorke. The anti-nociceptive activity was evaluated using acetic acid-induced writhing and hot plate tests in mice, while the anti-inflammatory activity was evaluated using carrageenan-induced hind paw edema model in rats. The oral median lethal dose of NLE was found to be greater than 5,000 mg/kg in rats and mice. NLE demonstrated significant and dose-dependent protection against acetic acid induced writhes and increased the reaction time of mice in hot plate test. Pretreatment of the animals with naloxone (2 mg/kg) significantly ( p < 0.05) attenuated the anti-nociception elicited by both NLE and morphine. NLE at the doses of 250 and 1,000 mg/kg significantly ( p < 0.05) decreased rat paw edema at the 2 nd hour in the carrageenan-induced paw edema test. The result of the study revealed that Nymphaea lotus possesses anti-nociceptive activities which may be mediated via the opioidergic system as well as mild anti-inflammatory activities thus providing scientific basis for the use of the plant in the management of pain and inflammatory diseases.