Abstract: Garden cress Lepidium sativum (LS) is an annual plant grown in many regions of Saudi Arabia. In the present study, LS collected from three regions of Saudi Arabia. Water suspension of seed powder was prepared from all samples and gavaged at different concentration (2, 4, 8 g/100/mL) to both adult female and male rats for 3 and 6 weeks, respectively. Blood samples from experimental animals were analyzed for liver functions tests and histopathology of the liver was conducted at the end of the study. Biochemical studies showed an increase in serum total protein with all doses. Albumin was increased at the high dose group however, AST, GGT were within normal levels. ALT and ALK were significantly increased after 3 weeks in males receiving 2 and 4 g kg^-1, respectively. Liver parenchyma in the form of vascular dilation and congestion of central and portal veins were observed in low doses (2 and 4 mg mL^-1) given for 3 weeks, High doses given for 3 weeks showed peri-portal fibrosis and peri-vascular edema. Bile duct proliferation was a prominent feature in those specimens. Congestion and focal cellular changes were less in samples taken after 6 weeks however, some hepatocytes showed signs of apoptosis. Individual variation was observed in response to dose and duration of feeding. Insignificant differences were showed concerning the sex of animals. Further investigation is needed to clarify the cytological and biological effects of feeding on LS using enzyme immunoassay and electron microscopic study of hepatic tissue.