Background: Alcohol is a central nervous system depressant, its abuse cause long-term changes in the brain. Aim of the Work: This work was performed to study the alcohol withdrawal effects and to evaluate the effects of baclofen administration in male albino rats. Materials and Methods: This study was carried out on 150 adult male albino rats which divided into 5 groups each of 30 rats;Group1 (negative control group), Group 2(positive control group),Group 3 (baclofengroup): each rat was gavaged orally with daily dose of 15mg/kg in the first 3 days and 30mg/kg for remaining of 4 weeks.Group 4 (ethanol group) each rat was gavaged orally with daily dose of 10 g/kg of 10% ethanol for 2 weeksthen withdrawn and continue without administrations for 4 weeks. Group 5 (ethanol and baclofengroup) each rat was gavaged orally with daily dose of 10 g/kg of 10% ethanol for 2 weeks then withdrawn for 24 hours then receive baclofen: daily dose of 15mg/kg in the first 3 days and 30mg/kg for the remaining of 4 weeks. Results: there was a significant increase in mean values of prolactin, leptin, cortisol, aldosterone, alanine aminotransferase (ALT), aspartate aminotransferase(AST), gamma-glutamyl transpeptidase (GGT), bilirubin and International normalized ratio (INR) and significant decrease in mean values of albumin in ethanol dependent group as compared to their corresponding values in control group. Upon administration of baclofen to ethanol dependent rats there was a non-significant decrease inthe mean values of prolactin and leptin, significant decrease inthe mean values of cortisol, aldosterone, ALT, AST, GGT, bilirubin and INR and significant increase in mean values of albumin when compared with ethanol dependent group. Microscopic examination of  studied organs,  liver specimens of ethanol dependent group revealed fat accumulation in hepatocytes, necrosis with degenerative changes, inflammatory cell infiltrate, fibrosis and bile duct proliferation.While, the pancreas specimens of the rats of this group revealed acinar inflammatory cell infiltrate, dilated blood vessels, necrosis, fibrosis and degenerative changes of islets of Langerhans. The brain specimens of the rats of this group revealed decreased thickness of pyramidal layer, abnormal blood vessels, neuronal loss and gliosis. Immunostaining for TGF β protein in liver specimens revealed increased expression of transforming growth factor (TGF β) protein in cytoplasm and for P 53 protein in pancreas specimens revealed attenuated expression of P 53 protein in nuclei. Upon administration of baclofen to ethanol dependent rats there was regression of these changes. Conclusion: it could be concluded that alcohol abuse induced hormonal disturbance evidenced by increased blood levels of prolactin, leptin, cortisol and aldosterone hormones, hepatotoxic effects evidenced by elevation of liver function tests and severe liver damage, in addition, pancreas and brain damage in adult male albino rats and baclofen administration after withdrawal of alcohol was efficient in suppression of alcoholic effect. Recommendation: it is recommended to increase public awareness regarding the health impact of alcohol abuse and the effect of baclofen on alcohol withdrawal.