Senna septemtrionalis (Viv.) H.S. Irwin & Barneby (Fabaceae) is a medicinal plant used as a folk remedy for inflammation and pain. The objective of this study was to evaluate the anti-inflammatory and antinociceptive actions of an ethanol extract of Senna septemtrionalis aerial parts (SSE). The in vitro anti-inflammatory effects of SSE were assessed using LPS-stimulated macrophages and the subsequent quantification of the levels of cytokines (IL-6, IL-1β, and TNF-α) with ELISA kits, nitric oxide (NO), and hydrogen peroxide (HO). The in vivo anti-inflammatory actions of SSE were evaluated with the TPA-induced ear oedema test and the carrageenan-induced paw oedema test. The antinociceptive actions of SSE (10-200 mg/kg p.o.) were assessed using three models: two chemical assays (formalin-induced orofacial pain and acetic acid-induced visceral pain) and one thermal assay (hot plate). SSE showed in vitro anti-inflammatory actions with IC values calculated as follows: 163.3 µg/ml (IL-6), 154.7 µg/ml (HO) and > 200 µg/ml (IL-1β, TNF-α, and NO). SSE showed also in vivo anti-inflammatory actions in the TPA test (40% of inhibition of ear oedema) and the carrageenan test (ED = 137.8 mg/kg p.o.). SSE induced antinociceptive activity in the formalin orofacial pain test (ED = 80.1 mg/kg) and the acetic acid-induced writhing test (ED = 110 mg/kg). SSE showed no antinociceptive actions in the hot plate assay. The pre-treatment with glibenclamide abolished the antinociceptive action shown by SSE alone. Overall, SSE exerted in vitro and in vivo anti-inflammatory actions, and in vivo antinociceptive effects by the possible involvement of ATP-sensitive K + channels.