Fructus Ligustri Lucidi has been used for its anti-inflammatory effects in traditional Chinese medicine. This study investigated the analgesic and anti-inflammatory effects of aqueous extracts of Fructus Ligustri Lucidi (AFLL) in mice. AFLL significantly inhibited the production of radicals and lipid oxidation in various models. The reference compounds present in AFLL, including quercetin, myricetin, caffeic acid, gallic acid and ellagic acid, exhibited the pharmacological activities by scavenging radicals and decreasing LPS-induced nitric oxide (NO) production in macrophages. Administration of AFLL showed a concentration dependent inhibition on the number of acetic acid-induced writhing responses and formalin-induced pain in the late phase, and paw edema development after Carr treatment in mice. The anti-inflammatory activities of AFLL could be via NO and tumor necrosis factor alpha (TNF-alpha) suppression and associated with the increase in the activities of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx). Western blotting revealed that AFLL decreased Carr-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expressions. These results suggest that anti-inflammatory mechanisms of AFLL might be correlated to the decrease in the level of malondialdehyde (MDA), iNOS and COX-2 in the edema paw via increasing the activities of CAT, SOD and GPx in the liver. Overall, the results showed that AFLL could serve as a natural source of antioxidant, analgesic and anti-inflammation.