Background:   Safe and effective method for contraception is still under continuous search. Injectable contraception is an attractive method and considers to be a suitable alternative for oral tablets. The use of the Medroxyprogesterone acetate (MPA) is a promising way for contraception due to its long mode of action and of minimal risk.  So this study was planned to evaluate the structural and histochemical changes induced by (MPA) in the liver of adult female rats as well as testing the degree of reversibility  of the changes that may develop after the arrest of its use. Material and methods:    Thirty adult female Albino Rats were used and divided into 3 groups: The first group was considered as a control group. The second group was injected intramuscularly with MPA 4 times with a dose of 2.7 mg/rat every three oestrus cycle. Liver samples were taken one day after the arrest of the last injection. The third group was treated as group two but liver samples were taken 30 days after the arrest of the last injection.  Indian ink injection was done in the abdominal aorta  for studying the distribution of the blood vessels in the liver. Paraffin sections were prepared and stained with Heamatoxylin and eosin and by PAS stain for structural changes and evaluating the amount of glycogen contents. Frozen sections were prepared for histochemical staining of both acid phosphatase and succinic dehydrogenase enzymes.   Results: The obtained results showed that the use of MPA causes marked vascular congestion in the hepatic vessels and it was of statistically significant when compared with that of the control. Such change was greatly improved after 30 days of the arrest of the injection.   Cellular hepatic changes were in the form of cellular hypertrophy and pale cytoplasmic staining. The cellular arrangement in the liver lobules was not altered.        Changes in the glycogen content showed marked increase in the content of its deposition and after the arrest of the injection it returns back to its normal values.   Histochemically it was observed no changes in the enzymatic contents in the liver cells for both acid phosphatase or succinic dehydrogenase enzymes especially when compared with the control date. Conclusions: It was concluded from this study that there were reversible structural and histochemical changes in the rat liver under the use of the MPA,  So it is concluded that the use of MPA could considered as a safe contraceptive method. This study advise the continuous check up  on the liver function during the use of such method.