In this study, the anticancer effect of prednisolone was investigated using rats with normal endogen adrenaline levels (intact), reduced adrenaline levels (metyrosine‐induced) and adrenaline deficiency (adrenalectomized) via gastric adenocarcinoma model. Gastric adenocarcinoma was induced with N‐methyl‐N′‐nitro‐N‐nitrosoguanidine (MNNG). According to our experimental results, prednisolone could not prevent MNNG‐induced adenocarcinoma when used alone in intact rats. There were neither macroscopic nor microscopic signs of cancer in the rat groups that received metyrosine and prednisolone. However, dysplasia occurred in the stomachs of 2 of 10 rats that received metyrosine and prednisolone. There was no adenocarcinoma genesis in the stomachs of adrenalectomized rats that received prednisolone alone. However, yohimbine (a selective blocker of α2‐adrenoreceptors) pretreatment in adrenalectomized rats negated the anticancer effect of prednisolone. In conclusion, prednisolone was shown not to be an anticancer agent in intact rats when used alone; however, it has anticancer effects in rats whose adrenaline levels were reduced via adrenalectomy or metyrosine, which is a catecholamine synthesis inhibitor.