Hydroxychloroquine (HCQ) is an effective drug for the treatment of various autoimmune disorders. It has appropriate pharmacological properties that show its effectiveness in improving the control of parasitic infections such as malaria. It is rapidly absorbed into the plasma and excreted through the kidneys. This study was designed to investigate the effect of hydroxychloroquine (HCQ) at two concentrations of 25 and 50 mg/kg/day on the histological structure of the kidney in an adult rabbit (Orectolagus cuniculus). The study was conducted on 18 rabbits, it was divided randomly and equally to three groups included a control group and a group that was treated with a concentration of 25 mg/kg/day of the drug, while the animals of the third group was injected with a dose of 50 mg/kg/day. The results of the histological study showed the occurrence of pathological histological changes to the kidneys in the group of animals treated with the drug of 25 and 50 mg/kg/day concentration, the most prominent of which was a clear congestion of blood in some blood vessels in the cortex area and between the epithelial cells lining the glomeruli. It also showed a clear cellular infiltration near the blood vessel. Degeneration of the lining of the epithelial cells of some renal tubules, especially the proximal convoluted tubules, and the separation of tubule cells from the detached basement membrane and their gathering in the lumen of the tubules in most tissue sections was observed. It was also found that the glomerulus was enlarged and that treatment with this drug led to a decrease in Bowman’s space, in addition to an increase in the thickness and density of the basement membrane of the urinary tubules. Glomerular cells suffered from accumulation, shrinking, enlargement capsular space, and cell death. It can conclude from the above results that the hydroxychloroquine drug has clear effects on the histological structure of the kidneys.