Abstract: Clarithromycin is a well established, semi synthetic, second generation macrolide antibiotic for respiratory, disseminated mycobacterial, skin and Helicobacter pylori infections. Although, this drug has proven to be relatively safe, hepatic dysfunction including increased hepatocellular and/or cholestatic hepatitis with or without jaundice has been infrequently reported with its use. This study was therefore designed to investigate the toxic potentials of two different doses of clarithromycin (Claricin ^®) in rats. About 30 rats (Wistar strain) weighing between 180-220 g were completely randomised into 3 treatment groups. Group 1 (Control) received physiological saline while group 2 and 3 were administered 8.8 and 17.6 mg kg^-1 of clarithromycin (Claricin ^®) respectively twice daily for 7 days. Total billirubin, creatinine and urea levels were significantly (p<0.05) elevated in the plasma of the rats that received the two doses of Claricin ^® by 62 and 94.6, 60 and 122% and 22 and 31.8%, respectively when compared to the control. Activities of ALP, ALT, AST and GGT were also significantly (p<0.05) higher in the plasma of animals treated with the two doses of the drug by 35 and 44.1%, 17 and 30.9%, 22 and 35.3% and 58 and 133.9%, respectively. Plasma lipid profiles revealed a significant increase (p<0.05) in total cholesterol, HDL cholesterol, LDL cholesterol and triglycerides in the two treated groups by 14 and 27.9%, 21 and 43.42%, 19 and 33.64% 15 and 46.2%, respectively. A significant (p<0.05) increase in the MDA level by 36 and 55%, respectively in the two treated groups was also observed. Furthermore, the two doses of clarithromycin significantly (p<0.05) reduced the hepatic levels of ascorbic acid and reduced glutathione (GSH) by 26.2 and 40% and 55 and 73%, respectively with a concomitant reduction in activities of hepatic GST by 23 and 36%, respectively. Similarly, there was a significant reduction in the activities of hepatic catalase and SOD by 46 and 51.9% and 34 and 52%, respectively in the clarithromycin treated groups. Liver histopathology revealed a mild periportal cellular infiltration by mononuclear cells and severe central venous congestion respectively in the two dose groups while foci of haemorrhages in the renal cortex were observed in the 17.6 mg kg^-1 Claricin ^® group. These data indicate that oral administration of clarithromycin has adverse effects on both enzymic and non-enzymic antioxidant status and induces oxidative stress as well as renal and liver damages in rats.