BACKGROUND Isoniazid is a drug for treatment of tuberculosis. One of the main side effects of this drug is hepatotoxicity, which is a major cause of treatment interruption in tuberculosis. This study is about the preventive effect of Salep on this side effect of isoniazid. METHODS This study is an experimental study in which the preventive effect of salep on isoniazid hepatotoxicity is evaluated. In this study 56 rats were randomly placed in 7 eight members groups including: control group, sham, isoniazid and four isoniazid/salep groups. At the end of the study the laboratory criteria and histological features of liver toxicity were compared in different mentioned groups. RESULTS Significant lower serum levels of liver enzymes, billirubin, MDA and TOC; and significant higher levels of TAC and total proteins, were revealed in isoniazid/salep group in compare to isoniazid alone group.In addition, histological studies had not showed liver injury in isoniazid/salep group, while there was significant liver injury in isoniazid alone group. CONCLUSIONS Orchid extract (salep), probably because of its antioxidant properties, prevent the destructive effects of isoniazid on the liver.