Resveratrol, an edible polyphenolic phytoalexin present in grapes and red wine, has been reported to inhibit proliferation and induce apoptosis of bladder cancer cells. In the present study, the molecular mechanisms of resveratrol on human bladder cancer cell apoptosis was examined. The effect of resveratrol on the viability and apoptosis of T24 and 5637 cells was measured using an MTT assay and flow cytometric analysis, respectively. Next, the effect of resveratrol on miR‑21 expression was detected by real‑time PCR. The expression of phospho‑Akt and Bcl‑2 following treatment with resveratrol or the downregulation of miR‑21 expression were also measured. Resveratrol induced the cytotoxicity and apoptosis of T24 and 5637 cells in a dose‑dependent manner. Resveratrol decreased the expression of miR‑21, the level of phospho‑Akt and Bcl‑2 protein expression. In addition, the downregulation of miR‑21 expression inhibited the level of phospho‑Akt and Bcl‑2 expression. Insulin‑like growth factor‑1 was able to reverse the effect of the miR‑21 inhibitor on Bcl‑2 expression and apoptosis in T24 and 5637 cells. Notably, overexpression of miR‑21 expression was able to restore the inhibition of Akt activity, downregulation of Bcl‑2 expression and apoptosis induced by resveratrol. Collectively, data revealed that the effect of resveratrol on bladder cancer cell apoptosis was due to miR‑21 regulation of the Akt/Bcl‑2 signaling pathway.