Methotrexate (MTX) is an antimetabolite of the normal folic acid produced by human and animal bodies. MTX antagonizes Folic Acid which is vital for purine and many vital amino acids. Treatment with MTX has been widespread all over the world recently. Physicians usually prescribe folic acid together or following treatment with MTX. Some patients minimize the importance of having folic acid with MTX or after it regarding it as a not essential drug as MTX. From here it comes, the value of this research to clarify the important role of folic acid in minimizing the side effects of MTX. In fact this effect applies on most systems in the human and animal bodies; however, authors prefer to focus on the neurological aspects as references are somewhat scarce especially in the veterinary aspect and found some behavioral changes which coincide with brain histopathological findings. Keywords: methotrexate, folic acid, neurological changes, rat
