Abstract: Foot-and-Mouth disease (FMD) is one of the world’s most important infectious animal diseases especially cloven-hooved livestock caused by picornavirus and responsible for huge global losses of livestock production and trade, as well as frequent and highly disruptive large-scale epidemics. Bee (Apis mellifera) venom therapy is an alternative form of healing to treat various diseases. Bee venom contains at least active components which have some pharmaceutical properties; the most significant components of bee venom which have antiviral properties like mellitin, phospholipase A2 (PLA2) and Protease inhibitor. Melittin is main active component and the powerful stimulator of phospholipase A2 that destroys phospholipids and dissolves the cell membrane of the agent. Protease inhibitor inhibits the activity of different proteases like trypsin, chymotprypsin, plasmin, thrombin, thus decreasing inflammation. In this work, Egyptian bee venom (Apis mellifera lamarckii venom) was obtained from VACSERA used as a treatment against FMDV-O in Egypt. There are improvements in hematological, biochemical and histopathological tests, the clinical signs are decreased in the treatment period and the virus load is more significance decreases. So this study proved that the bee venom used as natural medicine has been developed to fulfill recent medical requirements without noticed side effects. Bees have been appreciated for their medicinal purposes as a treatment for many diseases and restoring the vitality of the body.