Objective To observe the effect of resveratrol proliferation of different estrogen receptor subtypes of MCF-7 cells, and to study the mechanism. Methods MTT assay and flow cytometry were carried out to examine the abilities of cell proliferation. Western blotting method was used to detect the changes of the signal pathway. Results The abilities of cell proliferation were ERα^-ERβ⁺-MCF-7＜MCF-7＜ERα⁺ERβ^--MCF-7. The S-phase of the ERα⁺ cell cycle was increased by resveratrol, however, ERβ⁺ cells was arrested at phase G₀/G₁. The protein expression of bcl-2, ERK-P and AKT-P were increased in ERα⁺ cells treated with RES. The effect of ERβ⁺ cells was opposite. Conclusions The dual regulatory effect on MCF-7 cells by resveratrol may be related to the affinity of different estrogen receptor subtypes.