Alteration in cytokine levels, particularly, IL-6, TNF-α IL-1β and IL-2, has been implicated in the pathogenesis of epilepsy and bipolar disorder. Lamotrigine (LTG), an antiepileptic drug with mood stabilizing properties, has documented immunomodulatory effects. However, its effect on cytokine secretion in vivo has not been examined. Besides, studies have reported inconsistent results of the in vitro effects of LTG on cytokine secretion. Hence, we used murine models of inflammation to characterize the in vivo and the in vitro effects of LTG on the secretion of the aforementioned cytokines, using ELISA. LTG significantly inhibited basal and mitogen-induced IL-6, TNF-α and IL-1β secretion in vivo and in LPS-treated RAW264.7 cells in vitro. In PMs, LTG inhibited basal and LPS-induced IL-6 and TNF-α secretion. Our findings extend the current understanding of the anti-inflammatory properties of LTG and may be relevant to its role in modulating the immune system in epilepsy and bipolar disorder. © 2018 Elsevier B.V.