The use of chemotherapeutics induces cardiotoxicity and affects immune functions, therefore development ofcombinatorial agents against cardiotoxicity and immunosuppression needs to be explored. Previous studies of thehexane insoluble fraction (HIF) of an ethanolic extract of Ficus septica leaves showed anticancer effects singlyand in combination with doxorubicin on T47D breast cancer cells. In this present study, it was evaluated for itsimmunomodulatory activities in doxorubicin-treated rats. Thirty male Sprague Dawley rats were divided intofive groups consisting of six rats each as follows: Group 1, receiving oral saline 10 ml/kg BW (control group);Group 2, receiving HIF dose 750 mg/kg BW orally, once daily; Group 3, receiving HIF dose 1.500 mg/kg BWorally, once daily; Group 4, given oral saline 10 ml/kg BW (normal group); Group 5, receiving HIF dose 1.500mg/kg BW orally, once daily. The rats of group 1-3 were intramuscularly administered with doxorubicin at adose of 4.67 mg/kg BW at the days 1 and 4 to suppress immune functions. Concomitantly, the rats were treatedwith saline or HIF for seven consecutive days (1 to 7). Treatment of HIF succeeded in reducing side effects ofdoxorubicin based on increasing lymphocyte density and phagocytosis activity and capacity of macrophages,as well as increasing the CD8+ blood level and decreasing spleen IL-10 expression. Hexane insoluble fraction ofof ethanolic extract of Ficus septica leaves has potential as a protective agent combined with doxorubicin.