The macrolide antibiotic tylvalosin tartrate is effective against mycoplasma, certain Gram-negative bacteria, and Gram-positive bacteria. It works by preventing the bacterial cell from producing new proteins. The purpose of this experiment was to investigate the effects of this antibiotic on the lungs, kidneys, and liver of broiler chickens. Twenty broiler chicks (Ross 308), 21 days old and weighing 600-800 gm, were split evenly into two groups: G1, the control group, and G2, the group that was treated with tylvalosin. The G1 group received 1 ml/kg of normal saline. While G2 group received 25 mg/kg of Tylvalosin. In the fourth day all birds were killed and 1 gm of tissues was taken from liver, lung and kidney for histopathological study. The histological changes in the liver from treated group showed inflammatory cell infiltration with massive area of hepatocyte necrosis, with micro aggregations inflammatory cell infiltration and cytoplasmic vacuolation, while the kidney of treated group showed massive tissue necrosis glomeruli and proximal tubule, acute cell swelling and inflammatory cell infiltrations. The lung of treated group showed epithelial cells degeneration and sever congested atria. In conclusion, tylvalosin cause damage to lung, hepatic and renal tissues when given to chickens at 25mg/Kg of body weight.