Objectives: The negative effects of alcohol on health have attracted attention in recent years. The most devastating complications of alcoholism, such as kidney damage, can be seen due to the continuous consumption of alcohol. Possible mechanisms by which alcohol may increase renal dysfunction have been expressed in the literature. Among these mechanisms, oxidative stress is thought to be a potential mechanism that affects kidney function. Nitric oxide synthase (NOS) and nuclear factor kappa B (NF-κB) levels, which have roles in oxidative stress and inflammation, may be at abnormal levels in the kidney in alcohol use disorder. This study aimed to evaluate the role of NOS and NF-κB molecules in the mechanism of kidney damage caused by alcohol use. Materials and Methods: The immunoreactivity of NOS2 and NF-κB in kidney tissue was evaluated in an experimental model of acute and chronic alcohol intake in male and female rats (n=56). Groups, control female, control male, sham female, sham male, acute male model, acute female model, chronic female model and chronic male model. The acute and chronic model groups were given ethanol to induce alcohol intake. Immunohistochemical analyzes were performed for NOS2 and NF-κB expressions along with histopathological analysis in kidney tissues. Results: It was observed that glomerulation degeneration, bleeding, vacuolization, and inflammation were increased in kidney tissues in all groups compared to control groups. In addition, NF-κB and NOS2 expressions were found to be significantly higher in the acute and chronic model groups compared to the control groups. Conclusion: The presented findings reveal that the expression of NOS2, which is involved in oxidative stress, and NF-κB, which is involved in inflammation, increases kidney damage in acute and chronic alcohol intake. Therefore, NFκB and NOS2 proteins, which play a role in tissue damage, inflammation, and oxidative stress response, may be associated with alcohol-induced renal damage.