Aim: In present study, the anti-inflammatory activities of a new series of benzimidazole derivatives were studied, investigating their inhibition of secretory phospholipase A₂, lipoxygenase, COXs and lipopolysaccharide-induced secretion of TNF-α and IL-6 in mouse RAW264.7 macrophages. Results: Synthesized compounds effectively inhibited proinflammatory enzymes and cytokines. Conclusion: A strong inhibition of secretory phospholipases A2 was exhibited by benzimidazole derivatives with trifluoromethyl and methoxy substitutions at position 4 of attached phenyl, whereas compound 8 containing pyridine ring substituted with amino group showed very potent 5-lipoxygenase inhibition. Molecular docking experiments were carried out to elucidate the molecular basis of the observed inhibitory activities.