Clomipramine is a tricyclic antidepressant commonly used to treat anxiety related behavioral disordersÂ in human and animals. The current study was performed to assess the effects of differentÂ therapeutic doses of clomipramine hydrochloride supplementation on hepato-renal functions, lipidÂ peroxidation, frequencies of micronucleated polychromatic erythrocytes in bone marrow,Â DNA damage in peripheral blood lymphocytes using the comet assay and effects of withdrawalÂ of the drug for 4 weeks on these parameters. Forty two Swiss albino male mice were divided intoÂ seven equal groups. The first group served as a control, while groups 2, 4 and 6 were orally treatedÂ with low (75 mg/kg of body weight), medium ((100 mg/kg of body weight), and high dosesÂ (250 mg/kg of body weight), respectively of clomipramine hydrochloride daily for 30 days. However,Â groups 3, 5 and 7 served as low, medium and high withdrawal groups for 4 weeks. DifferentÂ therapeutic doses of clomipramine hydrochloride resulted in a significant increase in the levels ofÂ serum ALT, AST, BUN and creatinine compared to control. Also, plasma malondialdehyde levelsÂ showed were significant increase in mice treated by different therapeutic doses of clomipramineÂ hydrochloride compared to control group. In contrast, the administration of clomipramineÂ hydrochloride in three therapeutic doses for 30 days caused a significant increase in the frequencyÂ of micronuclei in polychromatic erythrocytes of mice bone marrow, this increase reached moreÂ than ten times the value determined before the treatment and directly proportional to the dose.Â The level of basal endogenous DNA damage measured as the mean of percentage of DNA in theÂ tail of the lymphocytes in mice treated by low, medium and high therapeutic doses of clomipramineÂ hydrochloride were significantly higher than in controls. However, in the recovery periodÂ (4weeks), a significant amelioration in all studied parameters was observed. Results indicatedÂ that, clomipramine is a hepato renal toxic drug and induces a significant amount of DNA damageÂ and in-vivo genotoxic drug.