Abstract: AIM To investigate the anti-tumorpromoting activity of dehydroepiandrosterone (DHEA) and its mechanism of action. METHODS Using croton oil-induced ear edema model and applying confocal laser scanning microscopy, flow cytometry, immuno fluorescent techniques to investigate the inhibitory effect of DHEA on tumor promotion. RESULTS DHEA 25 mg·kg^-1 was shown to inhibit croton oil induced ear edema in mice by 51%. DHEA at dose of 40 mg·kg^-1 and 10 mg·kg^-1 exhibited inhibitory effects on croton oil-induced ornithine decarboxylase (ODC) activity by 64% and 53%, respectively. These results revealed that DHEA can block the change of cell cycle and the percentage of S phase was decreased to 17% at concentration of 10^-7 mol·L^-1 . The increase of Ca²⁺i and pH as well as PKC-activation induced by TPA stimulation were significantly inhibited by DHEA pretreatment. CONCLUSION The present experiments demonstrate that DHEA appears to be an attractive candidate as an anti-tumorpromotion agent for tumor chemoprevention. The mechanism of its action might be related to its inhibitory effects on ODC activity and Ca²⁺ DG PKC signal pathway.