Nigella sativa (NS) is an herbal plant commonly cultivated in many Asian countries but the products are exported to different parts of the world including Nigeria. The medicinal effects of the plant have been the subject of many scientific researches. The oil derived from its seed had been shown to possess anti-inflammatory (Mutabagani et al., 1997), and anti-pyretic (Ashour et al., 2006) activities among others. In this study, the effect of NS oil on inflammation and the nitric oxide (NO) system was investigated. Chronic inflammation was induced using formaldehyde as described by Owoyele et al., 2010. In this model, wistar rats (120-150g) were divided into four groups of five animals each as follows: Grp A, B, C, and D, they were administered normal saline, indomethacin (5mg/Kg), NS oil (1ml/Kg), and NS oil (2ml/Kg) orally respectively. Two models of acute inflammation, carrageenan and histamine-induced paw oedema were employed using methods described by Winter et al., 1962 and Perianayagam et al., 2006 respectively. The animals were divided into five groups of five animals each as follows: Grp A, B, C, D, and E, they were administered normal saline, indomethacin (5mg/Kg), L-NAME (100mg/Kg), NS oil (1ml/Kg), and NS oil (2ml/Kg) orally respectively. To check for the involvement of nitric oxide, the experiment was repeated (employing the acute inflammatory models) with L-arginine administered intraperitonially to all groups 1hr after inflammation induction. Change in paw circumference (oedema) after inducing inflammation was measured daily for the 10-day duration of the chronic inflammatory model and hourly for the 6-hour duration of the acute inflammatory models. Arthritis in the chronic inflammatory model was significantly reduced (P< 0.05) from 3.40 ± 0.37 to 0.80 ± 0.01mm, and 5.40 ± 0.78 to 1.00 ± 0.02mm in the groups that received indomethacin, and NS oil (2ml/Kg) respectively. In the carrageenan model, oedema reduced significantly (P< 0.05) from 1.60 ± 0.24 to 2.80 ± 0.20mm, and 1.80 ± 0.37 to 2.60 ± 0.24mm in the groups that received L-NAME, and NS (2ml/Kg) respectively. In the histamine model, oedema reduced significantly (P< 0.05) from 1.40 ± 0.22 to 3.00 ± 0.43mm, and 3.00 ± 0.19 to 4.80 ± 0.36mm in the groups that received L-NAME, and NS (2ml/Kg) respectively. Oedema further reduced significantly (P< 0.05) upon administration of L-arginine in groups that received normal saline and NS oil. The result showed that NS oil and nitric oxide worked in synergy, producing an additive effect on the anti-inflammatory activity of NS oil. It is hereby concluded the anti-inflammatory effect of NS oil may be enhanced by nitric oxide synthase