The dose-dependent effect of progesterone on PI3K/AKT signaling pathway, which plays a vital role in regulating various biological processes in human breast cancer, is not well defined. Herein, we analyzed the dose-associated influence of progesterone on AKT activation in human breast cancer cells. MCF-7 cells were treated with progesterone at a concentration ranging from 10-10 M through 10-6 M for 30 minutes and the extent of AKT phosphorylation was assessed using western blotting. Treatment with progesterone at various concentrations led to AKT phosphorylation in these cells. Notably, AKT activation, when treated with lower doses of progesterone was higher than that observed upon treatment with higher doses. Pre-treatment with PI3K inhibitor (LY294002) attenuated progesterone-induced AKT activation in a parallel manner over the range of progesterone doses administered. RU486, which is a progesterone receptor antagonist, induced AKT phosphorylation. These results suggest that progesterone seems to induce dose-dependent differential activation of PI3K/AKT pathway in MCF-7 cells.