It has been suggested that high fat (HF) diet exaggerates the stress-induced release of glucocorticoids due to activation of the hypothalamic-pituitary-adrenal (HPA) axis. In an initial experiment, where rats were fed HF diet for 4 days, we found that HF-fed controls stopped gaining weight indicating that they were hyper-responsive to the mild stress of tail bleeding but responded the same as low fat (LF) fed rats to the more severe stress of restraint. A second experiment confirmed these results when rats fed HF diet for 4 days showed an exaggerated corticosterone release in response to an i.p. injection of saline and movement to a novel cage, compared to LF-fed rats. Experiment 3 tested the same parameters as Experiment 2 but interchanged the diets. This allowed us to differentiate between the effects of the dietary fat and the novelty of the diet. Additionally this experiment determined whether hyper-responsiveness to mild stress in HF-fed rats was sustained during a prolonged exposure to diet. The results confirmed that HF diet, not novelty, exaggerated the endocrine stress response after 9 days on diet but that the effect was no longer present after 23 days on the diet. The hyper-responsiveness of the HPA axis in HF-fed rats is similar to that observed in animals that have been exposed to a significant chronic or acute stress, suggesting that HF diet may initially be perceived as a stressor.