Recently, the use of dietary nucleotides has mentioned in aquaculture, due to improvement in immune system, increasing growth parameters and absorption in the intestine. In general, nucleotides nearly, affect all cellular processes and play an important role in structural and regulatory functions of the body. Nucleotides continuously are synthesis, degradation and recycling in the cell. The immune system cell such as lymphocytes, red blood cells, hematopoietic cells and intestinal mucosa due to rapid metabolism and fast reaction, also need to high level of nucleotide, have a very limited capacity for nucleotide synthesis. In these cells, exogenous nucleotide administration, is very important for normal functions. Over the past two decades, use of nucleotides in diets has been examined for improving the immune system against viruses, bacteria and parasites, liver function, increased levels of absorption in the intestine and growth, fat and protein metabolism, biochemical and physiological functions and improve the stress response in marine animals. In addition, these compounds are important to energy transmission. Their effect on maturation, activation and phagocytosis of macrophages in humans and animals have been reported. There is a little information about their physiological functions in fish and more research is needed in this area.