Rabies is considered one of the most harmful viral infections of warm-blooded animals still. Thousands of people are infected with it each year worldwide. It is a fatal disease unless early treatment is received before the appearance of symptoms. About, 24,000 people die due to rabies in Africa each year and the infection is mainly transmitted by dogs. Fortunately, it could be prevented through vaccination. The importance of vaccination comes from that t is the only way to limit disease mortality levels, also the same vaccine is used for pre & post-exposure to rabies, therefore, high-quality control must be applied to it to ensure its safety, efficacy, and potency. A potency test is an important tool for experiencing the actual relative strength of manufactured assembly lots of vaccines. Because of the high variability of biological products, a potency is an effective tool that assures the lot-to-lot consistency of commercial vaccines. In this review, we aimed to discuss the rabies virus and its structure, different vaccine preparations, quality control of vaccines, different methods used in potency tests for rabies vaccine preparations including in vivo and invitro methods. In conclusion, without good quality control, we couldn't ensure consistency in vaccine manufacturing, and without replacement of old methods depending on animals, we couldn't go with global approaches of refinement, reduction, and replacement of animals in quality control tests especially the potency test.