Gout is an in ammatory arthritis characterized by the deposition of monosodium urate (MSU) crystals in the joints or soft tissue. MSU crystals are potent in ammation inducers. Melatonin (MLT) is a powerful endogenous anti-in ammatory agent and effective in reducing cellular damage. In the present study, possible underlying mechanisms associated with anti-in ammatory and anti-oxidative effects were investigated in rats with gouty arthritis and melatonin deprivation treated with MLT. Fifty-six rats were divided into seven groups: control, sham control, pinealectomy (PNX), MSU (On the 30th day, single dose 20 mg/ml, intraperitoneal), MSU+MLT (10 mg/kg/day for 30 days, intraperitoneal), MSU+PINX and MSU+PINX+MLT. PNX procedure was performed on the rst day of the study. As compared to the controls, the results showed that MSU administration caused signi cant increases in oxidative stress parameters (malondialdehyde and total oxidant status). Besides, signi cant decreases in antioxidant defense systems (glutathione, superoxide dismutase and total antioxidant status were observed. A statistically signi cant increase was found in the mean histopathological damage score in the groups that received MSU injection. It was found that histopathological changes were signi cantly reduced in the MSU+MLT group given MLT. In our study, it was determined that many histopathological changes, as well as swelling and temperature increase in the joint, which are markers of in ammation, were signi cantly reduced with MLT supplementation. These results suggest that melatonin ameliorates MSU-induced gout in the rat through inhibition of oxidative stress and proin ammatory cytokine production.