Ochratoxin A is a natural secondary product by several fungi of the genera Aspergillus Penicillium in different agriculture commodities. It causes great economic losses and health hazard to human and farm animals. This work was planned to study the induction of some chromosomal abnormalities that caused by ochratoxin A such as ring chromosome, acentric chromosome, dicentric chromosome, deletion, aneuploidy, and polyploidy and diminish these variations by using the black seed (Nigella sativa) in Balb/c mice. The results of the in vivo study are summarized as follows: 1.The amount of ochratoxin A produced by the isolate of Aspergillus ochraceus on corn as a substrate ranged between 47 - 50 ppb. 2. The treatment of mice with crude ochratoxin A by oral route caused signs of marked increase in body weight, blindness, hair loss, dyspnea, emaciation, irritation around the neck and shivering before death. 3. Short term culture for blood and spleen cells was used for chromosomal analysis to estimate the genotoxic effect of ochratoxin A and the treatment and the prophelacting effect of the black seed. 4. Genotoxic effects due to ochratoxicosis that observed on blood and spleen cells of mice included many chromosomal aberrations such as (chromosome chromatid breaks, ring chromosome, acentric chromosome, dicentric chromosome, aneuploidy, polyploidy deletion), these genotoxic effects of ochratoxin A observed in blood and spleen cells of mice were dose dependent. 5. Ochratoxin A contaminated diet also showed genotoxic effects in blood and spleen cells of mice including (ring chromosome, deletion, acentric chromosome, dicentric chromosome, polyploidy). 6. Black seeds contained high activity in diminishing the percentage of different hromosomal aberrations (ring chromosome, chromatid braek, and acentric chromosome) detected in mice blood and spleen cells