The changes in the antioxidant markers and histopathology in both adult male and female wistar rats fed with Calabash Chalk (nzu) was investigated. Twenty (20) wistar rats weighing between (120-150 g) were used for this study. They were randomly divided into four (4) Groups containing five (5) animals each (n=5) A-D. Groups (B-D) were fed with 1.0%, 2.0% and 8.0% of clay. Group A, not fed with clay served as control. After 21 days of continuous feeding, the animals were sacrificed and their liver organs excised for the following antioxidant markers (Catalase CAT, Reduced Glutathione GSH, Superoxide dismutase, SOD) and histopathology. The results showed significant (p< 0.05) increase in catalase activity in rats fed with 1.0% and 8.0% clay compared to control (0 clay) and group fed with 2.0%. However, no significant (p>0.05) difference was obtained for the group fed with 2.0% when compared to control.  The results obtained for GSH and SOD also showed no significant (p>0.05) difference in the fed groups when compared to control. Histopathological changes indicated mild periportal and intraparenchymal inflammation in group fed with 8.0%. From the study it can be deduced that clay consumption has the potential to elicit the activities of antioxidant markers and subsequent depletion providing weak defenses against reactive oxygen species (ROS) and liver damage in the rats.