Abstract: The consumption of a large quantity of alcohol over a relatively short time is an increasingly important public health issue. Syzygium cumini has anti-inflammatory and antioxidant properties. Hence, this study aimed to investigate the activity of the enzyme adenosine deaminase and the release of inflammatory mediators in an animal model of acute ethanol intoxication. We also investigated the possible beneficial effects of an aqueous leaf extract of S. cumini (ASc). To address this issue, two groups of rats received a single oral dose of ethanol (5 g kg–1). After 30 min, a group was treated with 0.4 g kg–1 of ASc. A control group and a group treated only with ASc were also included. After 6 h, we found that the acute administration of ethanol increased ADA activity in serum and in spleen lymphocytes and the IL-1, IL-6, TNF-α, INF-γ and NOx serum levels. Moreover, ethanol decreased the levels of IL-10 and ADA activity in the cerebral cortex. The ASc was effective in reversing the changes in ADA activity and in the levels of NOx and IL-10. In conclusion, our results suggest that the effect on the purinergic system is one of the mechanisms by which ethanol exerts its effects on the inflammatory mediators and on the central nervous system. The results also highlight the potential effect of S. cumini treatment in ameliorating changes caused by acute ethanol intoxication.