We investigated possible mechanisms of analgesic and anti-inflammatory activities of the methanol extract from the leaf of Elaeagnus oldhamii Maxim. (EO(MeOH)). EO(MeOH) was evaluated for its analgesic activity in acetic acid-induced writhing response and formalin test, and anti-inflammatory effect was examined by λ-carrageenan-induced paw edema assay. We detected the activities of GPx, GRd and SOD in the liver, and the levels of inflammatory mediators including IL-1β, IL-6, TNF-α, COX-2, MDA and NO in the edema paw to investigate the mechanism of action against inflammation. Total polyphenol, flavonoid and flavanol contents of EO(MeOH) were detected to explore its antioxidant activities. Results showed that, in the analgesic test, EO(MeOH) decreased acetic acid-induced writhing response and the licking time in the late phase of formalin test. In the anti-inflammatory test, EO(MeOH) decreased paw edema at the 2nd, 3rd, 4th and 5th h after λ-carrageenan had been injected. EO(MeOH) increased the activities of SOD and GPx in liver tissue and decreased MDA, NO, IL-1β, IL-6, TNF-α and COX-2 levels in paw edema tissue at the 3rd h after λ-carrageenan-induced inflammatory reaction. EO(MeOH) exhibited abundant polyphenol, flavonoid and flavanol contents. In HPLC fingerprint test of EO(MeOH), two index ingredients, ursolic acid and pomolic acid, were isolated from EO(MeOH) and were exhibited in HPLC chromatographic analysis. The results demonstrated analgesic and anti-inflammatory effects of EO(MeOH). It was indicated that the anti-inflammatory mechanism of EO(MeOH) may be due to declined levels of NO and MDA in the edema paw through increasing the activities of SOD, GPx and GRd in the liver. Additionally, EO(MeOH) decreased IL-1β, IL-6, TNF-α and COX-2 levels in the edema paw. The results suggested its value in future development of herbal medicine for the treatment of inflammatory diseases.