Progesterone (PG) is a steroid hormone that regulates normal reproductive functions including uterine and mammary gland development. The PG receptor belongs to the nuclear receptor superfamily of ligand dependent transcription factors that mediates gene expression, however, it also promotes cell signaling pathways through a non-genomic pathway including the activation of PI3K/Akt and Src/ERK1/2 pathways. However the role of PG in NFκB-DNA complex formation remains to be studied. We demonstrate here that PG induces Akt2 activation and an increase of NFκB DNA binding activity in MCF-7 breast cancer cells. Akt2 activation requires PI3K activity, whereas increase of NFκB DNA binding activity requires PI3K, mTOR, Akt, Src, and G-proteins activity, as well as the integrity of cytoskeleton. In summary, our findings demonstrate that PG induces an increase of NFκB DNA binding activity in MCF-7 cells.