The present study was designed to evaluate effect of caffeine to gamma irradiated rats. Forty eight female albino rats (120-150 gm) were divided into four groups (each of them 12 rats). The first group was considered as control. The animals in the second group were injected I.P. with caffeine (80 mg/Kg b.w.), the third group exposed to (7Gy) -radiation while the animals in the fourth group injected I.P with caffeine (80 mg/Kg. b. w.) 1 h prior to wholebody dose of -rays (7 Gy). Fresh liver specimens were obtained after 1 and 3 days of treatment. Paraffin sections were prepared for histological study (Hx & E.) and frozen sections were prepared for histochemical study for localization of both acid, alkaline phosphatases and succinic dehgdrogenase enzymes. The enzymatic activity was quantitatively evaluated and statistically analyzed. The obtained results showed that whole body -irradiation of rats induced definite microscopic changes in the liver represented by periportal fibrosis with some necrotic hepatic tissue. Meanwhile caffeine alone showed histological pattern more or less near to normal. On the other hand -rays combined with I.P. injection of caffeine revealed vaculated hepatocytes with dilated blood sinusoids. Histochemical changes were also observed showing significant increase in both acid phosphatase and succinic dehydrogenase enzymes activity after one and three days post exposure while the alkaline phosphatase enzyme activity showed significant decrease after one day and increase after three days of exposure. Administration of caffeine (1, 3, 7-trimethylzanthine), a major component of coffee (80 mg/Kg body weight), 60 min prior to whole body lethal dose of gamma-irradiation (7 Gy) resulted in improvement of the radiation induced changes in the activity of measured enzymes