Aluminum phosphide (AlP) is a cheap, effective, and commonly used agricultural pesticide. The present experiment was undertaken to investigate the effect of melatonin against aluminum phosphide -induced renal toxicity in rats. Forty male rats were divided into four groups. group I: rats maintained as control, group II: rats received melatonin, group III: rats received AlP, group IV: rats received AlP and melatonin with same previous doses. Data showed that AlP “GIII" treatment resulted in a significant increase in serum creatinine and urea level. Also, a markedly significant increase in lipid peroxidation (MDA). On the other hand, the administration of AlP causes a significant decrease in enzymatic antioxidants activities (superoxide dismutase, catalase, glutathione peroxidase glutathione reductase, and glutathione-S-transferase) in the kidney. The histopathological examination of a kidney of AlP -treated group rats, revealed kidney injury with necrotic changes, enlargement of many glomeruli, tubular dilatation, and leukocytic infiltration. Electron micrographs of the renal corpuscle showed obvious signs of injury, focal segmental thickening, and podocyte changes, mesangial cells appeared highly deteriorated. Also, proximal convoluted tubules lining cells revealed tremendous alterations and abnormalities in architectural features, an increasing number of the irregular shape of mitochondria with fragmented cristae. Moreover, kidney tissues showed markedly higher p53 induction. Additionally, treatment with melatonin alleviates the nephrotoxicity of AlP by significantly renormalize the Serum enzymatic and biochemical parameters. The biochemical results were supported by histopathological and ultrastructural observations of the kidney. Moreover, inhibition of p53 with melatonin was seen. From these results, it could suggest that melatonin might be useful for preventing nephrotoxicity caused by aluminum phosphide through ameliorative effects on (especially parameters) biochemical indices, oxidative stress, histological and ultrastructural changes.