In this study, we aimed to investigate the anti-inflammatory activity, antinociceptive activity and the action mechanism of Trachelospermi caulis extract. The anti-inflammatory effects were investigated using arachidonic acid, 12-O-tetradecanoylphorbol 13-acetate or carrageenan-induced oedema assays. Antinociceptive activity, using the acetic acid-induced writhing model, was also tested in mice. The extract exhibited dose-dependent and significant (P & 0.05 at 100–400 mg kg−1) anti-inflammatory and antinociceptive activity in the animals. To further understand the mechanism of activity, we investigated whether the extract inhibited the expression of inducible nitric oxide synthase (iNOS), the production of nitric oxide (NO) and the expression of TNF-α from murine macrophage RAW 264.7 cells. Similar to the in-vivo activity, the iNOS expression, NO production and TNF-α expression were found to be dose dependent and significantly suppressed by the extract through the inhibition of the p38 MAP kinase/NF-κB pathway. Taken together, the results presented here suggest that T. caulis extract may be useful for the treatment of various inflammatory diseases.