Background: Clarithromycin is a macrolide antibiotic used to treat common infections including respiratory tract, skin and Helicobacter pylori. This work investigates whether the administration of clarithromycin to pregnant females during the cleavage phase of gestation was associated with a risk of miscarriages and offspring morphological malformation and skeletal anomalies, histological changes and DNA fragmentation of embryos and liver of pregnant rats. Two major groups of pregnant albino rats were used. The animals of the control group received distilled water from the 1^st to 7^th days of gestation.One subgroup (C1) was sacrificed on the 8^th day; and the other (C2) was sacrificed on the 20^th day of gestation. The treated group was drenched 45 mg/kg clarithromycin (therapeutic dose) suspension from 1^st to 7^th day of gestation. The first subgroup (T1) was sacrificed on the 8^th day and the other (T2) was sacrificed on the 20^th day of gestation. Results: The obtained results showed a decrease in maternal body weight gain, increase in the rate of abortion, resorption and growth retardation of fetuses and some malformation in the skeletal system of the treated group. Histopathological studies of pregnant and fetal rats revealed congestion and dilatation of the central vein, fatty degeneration of the hepatocytes and severe DNA fragmentation.