Dietary supplementation with long-chain polyunsaturated fatty acids (PUFAs) has become an attractive possibility to alleviate or prevent cerebrovascular pathophysiology. To characterize the potentially beneficial cerebrovascular action of n-3 PUFAs that predominantly occur in fish oil, we set up an experimental paradigm where rats with chronic cerebral hypoperfusion were supplied with n-3 PUFA-enriched diets. Cerebral hypoperfusion was created by a permanent, bilateral occlusion of the common carotid arteries (2VO) of rats at the age of 4 months, with a survival of 3 months. Simultaneously, the rats were provided with experimental diets from the time of weaning until the termination of the experiments. The control diet was comparable to standard rat chow, while diet 1 contained additional n-3 PUFAs and diet 2 was further enriched with structural phospholipids and neurotransmitter precursors. In summary, the data show that diet 2 improved spatial learning of 2VO rats in the Morris water maze. Both diet 1 and diet 2 augmented blood-brain barrier parameters and increased the density of the M1-type muscarinic cholinergic receptors in the hippocampus independent of the rate of cerebral perfusion. In addition to an overview of these results, changes that were supportive or accompanying those described in the CNS are also presented. Briefly, plasma corticosterone concentration was elevated most explicitly by 2VO, while the relative weight of the liver and spleen increased due to the diets. The data draw attention to changes not only in the CNS, but also in the periphery as a consequence of chronic supplementation with n-3 PUFA-enriched diets.