Background and purpose:  We investigated the effect of nitric oxide synthase (NOS) inhibition on polymorphonuclear cell (PMN) influx in zymosan or lipopolysaccharide (LPS)‐induced arthritis and peritonitis. Experimental approach:  Wistar rats received intra‐articular (i.art.) zymosan (30–1000 µg) or LPS (1–10 µg). Swiss C57/Bl6 mice genetically deficient in intercellular adhesion molecule‐1 (ICAM‐1−/−) or in β2‐integrin (β2‐integrin−/−) received zymosan either i.art. or i.p. PMN counts, leukotriene B4 (LTB4), tumour necrosis factor‐α (TNF‐α) and interleukin‐10 (IL‐10) levels were measured in joint and peritoneal exudates. Groups received the NOS inhibitors NG‐nitro‐L‐arginine methyl ester (LN), nitro‐L‐arginine, N‐3‐(aminomemethyl)benzyl acetamide or aminoguanidine, prior to zymosan or LPS, given i.p. or s.c. in the arthritis and peritonitis experiments respectively. A group of rats received LN locally (i.art. or i.p.), 30 min prior to 1 mg zymosan i.art. Key results:  Systemic or local NOS inhibition significantly prevented PMN migration in arthritis while increasing it in peritonitis, regardless of stimuli, concentration of NOS inhibitors and species. NOS inhibition did not alter TNF‐α and IL‐10 but decreased LTB4 in zymosan‐induced arthritis. LN administration significantly inhibited PMN influx into the joints of ICAM‐1−/− and β2‐integrin−/− mice with zymosan‐arthritis, while not altering PMN influx into the peritoneum of mice with zymosan‐peritonitis. Conclusions and implications:  Nitric oxide has a dual modulatory role on PMN influx into joint and peritoneal cavities that is stimulus‐ and species‐independent. Differences in local release of LTB4 and in expression of ICAM‐1 and β2‐integrin account for this dual role of NO on PMN migration.