Objective: This study assessed and compared in vivo anti-inflammatory activity of Hippophae rhamnoides (HR) and Hippophae salicifolia (HS) seed oil. Materials and Methods: HR and HS seed oil was extracted by Soxhlet apparatus and characterized using gas chromatography mass spectroscopy. Wistar rats were used for predicting anti-inflammatory activity. Results: HR and HS (2 and 4 ml/kg, respectively) exhibited dose-dependent inhibition of carrageenan-, histamine-, prostaglandin-, bradykinin-, and arachidonic acid (AA)-induced paw edema. Significant leukotriene-induced inhibition was observed in HR. Myeloperoxidase (MPO) and lipid-peroxidase (LPO) assays were performed and HR and HS seed oil significantly decreased the level of MPO and LPO at 4 ml/kg dose (P Abbreviations Used: AA: Arachidonic acid, ALA: Alpha linolenic acid, COX: Cyclooxygenase, EPA: Eicosapentaenoic acid, GCMS: Gas chromatography-mass spectroscopy, HR: Hippophae rhamnoides, HS: Hippophae salicifolia, ip: Intraperitoneal, LOX: Lipoxygenase, LPO: Lipid peroxidase, LTB4: Leukotriene B4, LTs: Leukotrienes, MPO: Myeloperoxidase, PGE2: Prostaglandin E2, PGs: Prostaglandins, PUFA: Poly unsaturated fatty acid, SBT: Seabuckthorn