OBJECTIVE : Blockage of the urinary tract is often connected with renal function impediment, including reductions in glomerular filtration rate (GFR) and the power to control sodium as well as water elimination through urination. Melatonin, known to be the primary product of the pineal gland, prevents renal damage caused by ischemic reperfusion. However, the effects of melatonin on urinary obstruction, as well as release of obstruction induced kidney injury are still largely unknown. The aim of present study was to investigate the effect of melatonin on mediating protection against renal injury triggered from either bilateral ureteral obstruction (BUO) or BUO release (BUO-R). METHODS : Adult male Sprague-Dawley rats (n = 60) were clustered into six treatment groups: sham treated-1; BUO-non-treated (24 h BUO only); BUO + melatonin; sham treated-2; BUO-48hR (24 h of BUO and then release for 2 days); and BUO-48hR + melatonin. Kidney tissues, blood and urine samples were obtained for further assessment. RESULTS : It was found that melatonin treatment remarkably promoted the recovery of the handling capacity of urinary excretion of water as well as sodium in BUO and BUO-48hR models. Melatonin treatment partially inhibited inflammatory cytokine expression and the downregulation of aquaporin (AQPs, AQP-1, -2 and -3) expression in these two models. Moreover, the cytoarchitecture of BUO rats exposed to melatonin was well preserved. CONCLUSIONS : Melatonin treatment potently prevents BUO or BUO-R induced renal injury, which may be partially attributed to restoring the expression of AQPs and inhibition of inflammatory response, as well as preserving renal ultrastructural integrity.