Background: Acalypha wilkesiana, commonly called Irish petticoat, is native to the South Pacific Islands and belongs to the family Euphorbiaceae. In traditional medicine practice, the leaves of A. wilkesiana are eaten as vegetables for the management of hypertension, being a diuretic plant. Aim: This study was conducted to evaluate the effects of extracts of A. wilkesiana leaves on activities of serum aminotransferases and bilirubin levels, which are indicators of liver function, in salt loaded rabbits. Materials and Methods: A total of 30 rabbits were randomly divided into five Groups (A to E) of six rabbits each and treated with salt loaded diet, aqueous extract (Group B) and ethanol extract (Group C) of A. wilkesiana leaves; continuous salt loading (Group A); salt loaded and nontreated (D); nonloaded (with salt) and nontreated (with extract) (E). Results: Salt loading resulted in a significantly (P < 0.05) higher serum alanine aminotransferases (ALT) and aspartate aminotransferases (AST), and a significantly (P < 0.05) lower serum direct bilirubin, when compared with the control. Treatment with A. wilkesiana leaf extracts, at a dose of 300 mg/kg body weight, resulted in a nonsignificantly (P > 0.05) lower serum total bilirubin and direct bilirubin, as compared with the control, in the salt loaded rabbits. Discussion and Conclusion: The use of A. wilkesiana leaf could be relatively safe considering its effects on serum ALT, AST, total and direct bilirubin of the experimental animals. Thus, it may be useful in the management of any possible deleterious effect of salt load to the liver.