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Leishmaniasis is a tropical parasitic disease that has become a major health challenge in many countries of the world. Not only has not been found any effective vaccine or treatment for the disease eradication, but also the advent of drug resistance is also increasing. Therefore, it is vital to take a precise attention to the physiochemical cycles of the Leishmania parasite and to identify its biochemical pathways. One of the most important biochemical pathways of host and parasite is the arginase and nitric oxide cycles. By using L-arginine, arginase plays an important role in the metabolic pathways, particularly in ornithine production, polyamines biosynthesis and cellular activities, including proliferation and cell survival. Furthermore, L-arginine, can act as a substrate for inducible nitric oxide synthase (iNOS), which leads to the synthesis of nitric oxide (NO), thereby activating the cellular immune system and clearing intracellular parasites. High Arginase activity reduces the parasite load inside the host cell, and since lymphocytes need L-arginine for their activity, its deficiency impairs the response of host immune cells. Also, parasites arginase alone can determine the fate of Leishmania parasite within the host cell. The aim of this study was to provide a comprehensive overview of various studies on the arginase activity of both parasite and host and its direct impacts on the immune system and pathogenicity of the Leishmania parasite.