One of the biggest problems and challenges in the development of new drugs and/or treatment strategies for AD is the difficulty of passing the drugs across the blood brain barrier (BBB). The use of nanoparticles in drug delivery therapy holds much promise in targeting remote tissues. The object of the proposed study is to illuminate how injection of silver nanoparticles in the brain lead to leaking on the BBB, and therefore elucidate the possibility of penetrating into the areas of the brain which are most damaged by AD. We investigated the ultrastructural distribution of nanoparticles (silver ion, 5 nm) in the rat brain hippocampal tissue one and four days after the intra-peritoneal (i.p.) injection. At the end of the experiment perfusion fixation brain tissue was collected for the future electron microscopic analysis. Control animals which received vehicle injection revealed typical ultrastructural morphology of brain microvessels and neurons as we described earlier. The animals that received nanoparticle injection showed different degrees of brain lesions after one and especially after four days. The vascular and neuronal damage correlates with the presence of nanoparticles in hippocampal tissue. After one and four days of silver injection, varying sizes of silver aggregates were seen throughout the neuronal cell bodies. The accumulation of the silver particles was also associated with the extracellular matrix, which was observed to coexist in the presence of a flake-like structure surrounding the neuronal tissue after four days of silver injection, and appeared to be a permanent feature of the hippocampal tissue. Our study indicates for the first time that i.p. injected silver nanoparticles are definitely able to cross the BBB and can penetrate into the cell cytoplasm and induce underlying cellular changes, which can be used for drug delivery. Further research in this area should include more specific cellular and subcellular mechanisms such as targeting mitochondria, which appears to be a main target for the cell viability, and therefore a prime target for selective treatment strategies.