This study examined the hepatic functions (Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP)), and histological changes in liver and kidney in imipramine -induced rabbits. Twenty adult mice were randomly divided into two groups comprising 10 mice each. Control group, received 1 ml normal saline 0.9%. Groups 2 received daily, 10 mg/kg of Imipramine for 21 days. Assessment of (AST,ALT, and ALP) were done by spectrophotometry, in addition to histological studies. There were significant changes in parameters for rabbits in group 2 compared to control group. The histopathological examination of renal tissue revealed lymphocyte infiltration, congestion, glomerulus and tubular damage. The tubular was containing hypertrophied epithelial cell which block the lumen. Brain tissues in groups 2 showed degeneration of pyramidal cells in the cortex, congestion of the blood vessels in the cortex and medulla. The cortex certain pyramidal cell with slight enlarged. Conclusion: Evidence of biochemical and histopath-ological affection of hepatic, renal and brain evoked by repeated administration of imipramine for long periods.