Flavonoids, natural compounds widely distributed in the plant kingdom, are reported to affect the inflammatory process and to possess anti‐inflammatory as well as immunomodulatory activity in‐vitro and in‐vivo. Since nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS) is one of the inflammatory mediators, the effects of the ethanol/water (1:1) extract of the leaves of Apium graveolens var. dulce (celery) on iNOS expression and NO production in the J774.A1 macrophage cell line stimulated for 24 h with Escherichia coli lipopolysaccharide (LPS) were evaluated. The extract of A. graveolens var. dulce contained apiin as the major constituent (1.12%, w/w, of the extract). The extract and apiin showed significant inhibitory activity on nitrite (NO) production in‐vitro (IC50 0.073 and 0.08 mg mL⁻¹ for the extract and apiin, respectively) and iNOS expression (IC50 0.095 and 0.049 mg mL⁻¹ for the extract and apiin, respectively) in LPS‐activated J774.A1 cells. The croton‐oil ear test on mice showed that the extract exerted anti‐inflammatory activity in‐vivo (ID50 730 μg cm⁻²), with a potency seven‐times lower than that of indometacin (ID50 93 μg cm⁻²), the non‐steroidal anti‐inflammatory drug used as reference. Our results clearly indicated the inhibitory activity of the extract and apiin in‐vitro on iNOS expression and nitrite production when added before LPS stimulation in the medium of J774.A1 cells. The anti‐inflammatory properties of the extract demonstrated in‐vivo might have been due to reduction of iNOS enzyme expression.