Purpose: To study the anti-inflammatory properties and mechanism of action of date seed extract in carrageenan-induced edema in rats. Methods: In this study with a pre-and post-test control group design, 30 Wistar rats were divided into six groups: Groups C1, C2, and C3 (given 1, 3, and 5 g/kg of soaked date seeds, respectively); positive control (PC, positive control given dexamethasone, 0.5 mg/kg dose), negative control (NC, edema induced by carrageenan), and healthy control (HC, no treatment). In groups C1-3, PC, and NC, carrageenan was administered intraperitoneally prior to date seed, PC and NC treatments. Prostaglandin E2 (PGE-2), cyclooxygenase (COX)-1, COX-2, interleukin (IL)-1β, and IL-12 were measured before and immdiate;y after treatment and compared between the groups. Results: Steeped date seed modulated inflammatory mediators by decreasing IL-1β, COX-1, COX-2, IL-12, and PGE-2 significantly (p < 0.05). Its indicated that the steeped date seeds down-regulate proinflammatory mediators in a manner similar to that of dexamethasone as positive control. Conclusion: Steeped date seeds possess anti-inflammatory activity similar to that of dexamethasone, through a mechanism involving decreases in pro-inflammatory mediators. Thus, date seeds is a potential source of herbal anti-inflammatory therapy.