This study investigated the effects of oral administration of Croton penduliflorus seed oil (CSPO) and Depo provera on liver and kidney function of pregnant rabbits. Graded doses of CSPO were suspended in 5% Tween 20 solution. Twenty-five pregnant Dutch-white rabbits at mid-gestation were allocated into 5 groups. Group 1 animals served as control and received 1ml daily of 5% Tween 20 while groups 2-4 received 50, 100 or 150 mg/kg body weight oral dose of CPSO for 10 consecutive days. Animals in group 5 received one intramuscular injection of 2.73 mg/kg of Depo provera. Withdrawal of treatment was followed by 18 hrs fast, and then sacrificed. Blood samples from fasted animals were collected from all groups and analyzed for liver and kidney function parameters. CSPO caused significant (P < 0.05) dose-dependent elevation of serum ALT, AST and ALP; dose independent but significant (P < 0.05) increases in urea, direct bilirubin and creatinine accompanied by a significant (P < 0.01) depression of total bilirubin levels of treated animals. Depo provera resulted in significant (P < 0.01) elevation of serum globulin and creatinine levels with significant (P <0.05) depression of total bilirubin. It had non significant effect on the serum electrolytes and marker enzymes. In conclusion CPSO may result in liver damage, biliary obstruction and impaired kidney function.