Increased levels of inflammatory cytokines after traumatic brain injury (TBI) can lead to brain edema and neuronal death. In this study, the effect of melatonin on pro-inflammatory (IL-1ß, IL-6, and TNF-α) and anti-inflammatory (IL-10) cytokines following TBI was investigated considering anti-inflammatory effect of melatonin. Male Wistar rats were divided into five groups: Sham, TBI, TBI+VEH (vehicle), TBI+5mg dose of melatonin (MEL5), TBI+20mg dose of melatonin (MEL20). Diffuse TBI was induced by Marmarou method. Melatonin was administered 1, 24, 48 and 72h after TBI through i.p. Brain water content and brain levels of pro-inflammatory (IL-1ß, IL-6 and TNF-α) and anti-inflammatory (IL-10) cytokines were measured 72h after TBI. The IL-1ß levels decreased in the TBI+MEL5 and TBI+MEL20groups in comparison to TBI+VEH group (p<0.001). The levels of IL-6 and TNF-α also decreased in melatonin-treated groups compared to control group (p<0.001). The amount of IL-10 decreased after TBI. But melatonin administration increased the IL-10 levels in comparison with TBI+VEH group (p<0.001). The results showed that melatonin administration affected the brain levels of pro-inflammatory and anti-inflammatory cytokines involving in brain edema led to neuronal protection after TBI.