Arsenic poisoning is caused by its exposure via drinking water and is considered as a worldwide problem. Exposure to arsenic has been linked with a myriad of possible health effects. The aim of the present investigation was to evaluate alterations in the blood serum indexes and histological changes in liver of male rats exposed to arsenic (50ppm) in their drinking water for eight weeks. Blood was collected for serum analysis of various indexes and the animals were sacrificed by cervical dislocation for the collection of their liver for histopathological studies. Almost all the serum indexes analyzed in the present study were altered significantly in the arsenic exposed animals. The damage in liver tissue was prominent and degenerative and necrotic changes were observed in almost every area of the tissue. The blood indexes studied herein may serve as potential biomarkers for arsenic induced hepatotoxicosis that may affect the general health of the animals. A well planed data base of regularly updated arsenic level of different areas of Saudi Arabia would help in processing the water and provide As free water for consumption and avoiding deleterious effects of As exposure through drinking water.