OBJECTIVE: To prepare Dexamethasone (Dex) nano-micelles (called Dex micelles for short), and to study its in vitro anti-tumor effect. METHODS: Using γ-PGA as carrier, DMSO as organic solvent, Dex micelles were prepared by dialysis method. The morphology, particle size, Zeta potential, PDI, CMC, drug-loading amount and entrapment efficiency (EE) of micelle were observed and detected. Drug release of Dex micelles and Dex were compared under pH 5.5, 7.4. The effects of free Dex, γ-PGA, Dex micelles and prednisolone (positive control) (0.05, 0.1, 0.2, 0.5, 1.0 μmol/ml) on the survival rate of human lung adenocarcinoma A549 cells were compared. The uptake amount of A549 cells to 0.5 μmol/ml Dex micelles and free Dex were compared at 4, 37 ℃. RESULTS: Prepared Dex micelles were spheroidal and completely round with particle size of (76.25±3.74) nm,Zeta potential of 5.0 mV, PDI of 0.163±0.38, CMC of 7.609 μg/ml, drug-loading amount of (9.56±0.92)% and EE of (89.25±1.36)%. Compared with free Dex, the duration of drug release for Dex micelles prolonged under pH 5.5, 7.4. When the concentration ranged 0.05-0.2 μmol/ml, the effects of free Dex, γ-PGA, Dex micelles and prednisolone on cellular survival rate had no statistically significant difference (P>0.05). When the concentration was 0.5, 1.0 μmol/ml,survival rate of A549 cells treated with Dex micelles was significantly lower than that treated with free Dex or prednisolone (P<0.05). At 4 ℃, the uptake amount of A549 cells to Dex micelles and free Dex had no statistically significant difference (P>0.05). At 37 ℃, the uptake amount of A549 cells to Dex micelles was significantly higher than that of cells to free Dex, and that of A549 cells to Dex micelles and free Dex at 4 ℃. CONCLUSIONS: Prepared Dex micelles can prolong the duration of drug release of Dex, and decrease the survival rate of A549 cells and cellular uptake efficacy.