The present work investigates the anti-inflammatory activity of alpha-linolenic acid (ALA) and linoleic acid (LA) using computational and experimental analysis. The binding affinity of ALA and LA was appraised for cyclooxygenase 1 (COX-1), cyclooxygenase 2 (COX-2), and 5-lipoxygenase (5-LOX) using AutoDock 4.2 and AutoDock Vina 1.1.2. Anti-inflammatory activity of ALA (2 and 4 ml/kg, i.p.) (55.65 % v/v) and LA (2 and 4 ml/kg, i.p.) (55 % v/v) was further assayed using the rat paw edema test against a variety of phlogistic agents including carrageenan, arachidonic acid, prostaglandin, and leukotriene, respectively. ALA (2 and 4 ml/kg, i.p.) and LA (2 and 4 ml/kg, i.p.) were further tested for their efficacy against complete Freund's adjuvant (CFA)-induced (0.05 ml) arthritis in albino rats. Following CFA-induced arthritis, ALA and LA were tested for their inhibitory proficiency against COX-1, COX-2, and 5-LOX in vitro. The present study commends that the anti-inflammatory potential of ALA could be attributed to COX inhibition, in particular, COX-2.