The main factors contribute to breast cancer development is the combination of exogenous and endogenous factors. Endogenous factors include both SIRT1 and NF-kB. Exogenous factor used in this research is 7.12 dimethylbenz(a)anthracene (DMBA). 1,2-epoxy-3[3-3[3,4-dimetoxy-phenil]-4h-1-benzophiran-4-on] propane (EPI) is a derivative of isoflavone generate from clove leaf oil. To examine the effect of EPI on SIRT1 and NF-kB expression in DMBA-induced Sprague Dawley (SD) rats, and the correlation between SIRT1 and NF-kB expressions. Tissue generated form 35 Sprague Dawley female rats aged 2 weeks old were used in this study. Those rats were divided into 7 groups (5 rats/group), namely normal control group; corn oil group; DMBA group; EPI treated groups with 1 mg/kgBW (EPI I), 2 mg/kgBW (EPI II), and 4 mg/kgBW (EPI III), respectively; and doxorubicin group. EPI and doxorubicin were administered from 1 st until 15 th week, while DMBA were administered from 3 rd until 9 th week. The paraffin block was prepared from all breast organ of the rats that terminated at the end of week 15 th. Examination of SIRT1 and NF-kB expression was performed using light microscope at 400x magnifications, after immunohistochemistry (IHC) staining. Expression level of SIRT1 and NF-kB were analyzed using IHC-profiler plug-in in ImageJ software. SIRT1 and NF-kB expression in EPI treated groups were not significantly different with the one in Doxorubicin group, but lower than DMBA group (p=0.000). There was a positive correlation between SIRT1 and NF-kB expression (p=0.001; r=0.773) in EPI-treated group. EPI was able to prevent an increasing of SIRT1 and NF-kB expression in SD model breast cancer that induced with DMBA. There is a positive correlation between SIRT1 and NF-kB expression in EPI-treated SD rats that were induced by DMBA. ABSTRAK Faktor utama penyebab kanker payudara adalah kombinasi faktor endogen dan eksogen. Faktor endogen antara lain adalah ekspresi SIRT1 dan NF-kB dan Faktor eksogen yang digunakan untuk penelitian ini adalah 7.12 dimethylbenz(a)anthracene (DMBA). 1,2-epoxy-3[3-3[3,4-dimetoxy-phenil]-4h-1-benzophiran-4-on] propane (EPI) merupakan turunan isoflavone yang disintesis dari minyak daun cengkeh. Untuk mengkaji pengaruh EPI dengan kelompok Doxorubicin, tetapi lebih rendah daripada kelompok DMBA (p=0.000). Terdapat korelasi positif antara tingkat ekspresi SIRT1 and NF-kB (p=0.001; r=0.773) pada kelompok perlakuan EPI. EPI dapat mencegah peningkatan ekspresi SIRT1 and NF-kB pada model tikus kanker payudara yang diinduksi dengan DMBA. Terdapat korelasi positif antara tingkat ekspresi SIRT1 and NF-kB (p=0.001; r=0.773) pada tikus model yang diberi EPI.